Abstract Objectives Predictions regarding the on-going burden of SARS-CoV-2, and vaccine recommendations, require an understanding of infection-associated immune protection. We assessed whether early COVID-19 provided protection against Omicron infection. Methods We enrolled a cohort of adults in Ontario, Canada, with COVID-19 prior to October 2020 (early infection, EI), and a matched cohort with COVID-19 testing and a negative PCR (non-EI). Participants completed baseline surveys then surveys every two weeks until January 2023. Multivariable Cox regression was used to assess factors associated with COVID-19 infection during the first 14 months of Omicron. Results Overall, 624 EI (70%) and 175 (77%) non-EI participants met criteria for analysis; 590 (95%) EI and 164 (94%) non-EI had received at least 2 COVID-19 vaccine doses prior to Omicron. Of 624 EI, 175 (28%) had one SARS-CoV-2 re-infection and 8 (1.3%) had two, compared to 84 (48%) non-EI participants with one, 5 (2.9%) with two and 1 (0.6%) with 3 infections (P < 0.0001). In multivariable analysis of risk factors for Omicron infection, the overall hazard ratio (HR, 95%CI) associated with EI was 0.56 (0.43–0.74); HRs for BA.1/2, BA.4/5 and mixed BA.5/BQ.1/XBB periods were 0.66 (0.45–0.97), 0.44 (0.28–0.68) and 0.71 (0.32–1.56). EI and BA.1/2 infection combined reduced later Omicron infection (HR 0.07 (0.03–0.21) compared to no prior infection. Older age, non-White ethnicity, no children in household, and lower neighbourhood income were associated with reduced risk of infection. Conclusions In our highly vaccinated population, early SARS-CoV-2 infection was associated with a 44% reduction in symptomatic COVID-19 during the first 14 months of Omicron, providing significant protection against re-infection for more than 2 years.

BACKGROUND:It is unclear whether antibiotics impact delirium outcomes in older adults with pyuria or bacteriuria in the absence of systemic signs of infection or genitourinary symptoms. METHODS:We registered our systematic review protocol with PROSPERO (CRD42023418091). We searched the Medline and Embase databases from inception until April 2023 for studies investigating the impact of antimicrobial treatment on the duration and severity of delirium in older adults (≥60 years) with pyuria (white blood cells detected on urinalysis or dipstick) or bacteriuria (bacteria growing on urine culture) and without systemic signs of infection (temperature > 37.9C [>100.2F] or 1.5C [2.4F] increase above baseline temperature, and/or hemodynamic instability) or genitourinary symptoms (acute dysuria or new/worsening urinary symptoms). Two reviewers independently screened search results, abstracted data, and appraised the risk of bias. Full-text randomized controlled trials (RCTs) and observational study designs were included without restriction on study language, duration, or year of publication. RESULTS:We screened 984 citations and included 4 studies comprising 652 older adults (mean age was 84.6 years and 63.5% were women). The four studies were published between 1996 and 2022, and included one RCT, two prospective observational cohort studies, and one retrospective chart review. None of the four studies demonstrated a significant effect of antibiotics on delirium outcomes, with two studies reported a worsening of outcomes among adults who received antibiotics. The three observational studies included had a moderate or serious overall risk of bias, while the one RCT had a high overall risk of bias. CONCLUSIONS:Our systematic review found no evidence that treatment with antibiotics is associated with improved delirium outcomes in older adults with pyuria or bacteriuria and without systemic signs of infection or genitourinary symptoms. Overall, the evidence was limited, largely observational, and had substantial risk of bias.

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.

Introduction Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity.Methods and analysis SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants.Ethics and dissemination The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks.Trial registration number ClinicalTrials.gov Registry (NCT06168474; www.clinicaltrials.gov).

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Background:People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population.Objective:The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination.Design:This is a prospective observational cohort study.Setting:Participating outpatient kidney programs within Ontario and British Columbia.Patients:Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T).Measurements:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity.Methods:Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose.Strengths and limitations:The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population.Conclusions:This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.

Abstract Background The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. Results A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19–related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Conclusions Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.)

Key Points Many patients with metastatic urothelial carcinoma are deemed cisplatin-ineligible because of reduced kidney function. Options include split-dose cisplatin or carboplatin. There was no significant association between regimen type and AKI. Alternative regimens were associated with higher risk of progressive disease. There is a need to revisit cisplatin eligibility criteria and develop strategies to optimize cancer treatment for patients with CKD. Background Cisplatin-based chemotherapy regimens remain the optimal first-line treatment for patients with metastatic urothelial carcinoma (mUC). However, many patients are deemed cisplatin-ineligible, predominantly because of reduced kidney function. Other treatment options include split-dose cisplatin, carboplatin, and non–platinum-based regimens. We compared the incidence of AKI and cancer outcomes within three chemotherapy regimens. Methods We conducted a single-center retrospective study of patients with mUC who received first-line chemotherapy from 2005 to 2019. We compared standard gemcitabine–cisplatin (gem-cis) with two alternative regimens: ( 1 ) gem-cis split-dose regimen (split) with cisplatin divided over days 1 and 8 and ( 2 ) combination of gemcitabine–carboplatin or single-agent gemcitabine (gem/gem-carbo). The primary outcome was Kidney Disease Improving Global Outcomes–defined AKI. Secondary outcomes included overall survival and progression-free survival. Results We identified 183 patients (98 gem-cis, 32 split, and 53 gem/gem-carbo). Median baseline eGFR in the gem/cis group was 78 ml/min per 1.73 m 2 (interquartile range, 66–91), in the split group 64 (48–77), and in the gem/gem-carbo 45 (33–57). There was no significant association between regimen type and incidence of AKI when adjusted for age, Eastern Cooperative Oncology Group, baseline eGFR, hypertension, diabetes, and visceral disease. The adjusted hazard ratios were 1.31 (95% confidence interval [CI], 0.61 to 2.78; P = 0.49) and 0.98 (95% CI, 0.46 to 2.07; P = 0.95) for split and gem/gem-carbo groups, respectively, versus gem-cis. Split and gem/gem-carbo regimens were associated with higher mortality and progressive disease relative to gem-cis with an adjusted hazard ratio of 1.54 (95% CI, 1.02 to 2.33; P = 0.04) and 1.96 (95% CI, 1.31 to 2.95; P < 0.01), respectively. Median progression free survival was 8.1 (interquartile range, 4.6–14.8), 6.1 (4.1–9.3), and 4.4 (2.3–8.6) months in the gem-cis, split, and gem/gem-carbo groups. Conclusions There was no significant difference in the incidence of AKI between the three regimens studied. However, standard gem-cis was associated with improved cancer outcomes. Novel regimens and kidney protective strategies are needed for patients with mUC with kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.

AbstractAmong outpatients with coronavirus disease 2019 (COVID-19) due to the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta) variant who did and did not receive 2 vaccine doses at 7 days after symptom onset, there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI, −4.68 to 3.50; P = .77) with SARS-CoV-2 cultured from 2 (7%) of 28 and 1 (4%) of 26 outpatients, respectively.

This article describes the results of environmental sampling in out-patient clinics where adults with human monkeypox were evaluated. Viral DNA was detected at low concentrations on high-touch surfaces. Hospital-grade cleaning wipes reduced environmental contamination, usually to undetectable levels.

BackgroundLarge observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting.MethodsWe conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir.ResultsThere were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths.InterpretationNirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.

OBJECTIVES:Diabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, the available studies lack detail on COVID-19 illness severity and measurement of relevant comorbidities. METHODS:We conducted a multicentre, retrospective cohort study of patients 18 years of age and older who were hospitalized with COVID-19 between January 1, 2020, and November 30, 2020, in Ontario, Canada, and Copenhagen, Denmark. Chart abstraction emphasizing comorbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poisson regression. The main outcome measure was in-hospital 30-day risk of death. RESULTS:Our study included 1,133 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients, respectively, had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older; have chronic kidney disease, cardiovascular disease, and higher troponin levels; and be receiving antibiotics, when compared with adults without diabetes. In Ontario, 24% (n=96) of adults with diabetes died compared with 15% (n=109) of adults without diabetes. In Denmark, 16% (n=12) of adults with diabetes died in hospital compared with 13% (n=29) of those without diabetes. In Ontario, the crude mortality ratio among patients with diabetes was 1.60 (95% confidence interval [CI], 1.24 to 2.07) and in the adjusted regression model it was 1.19 (95% CI, 0.86 to 1.66). In Denmark, the crude mortality ratio among patients with diabetes was 1.27 (95% CI, 0.68 to 2.36) and in the adjusted model it was 0.87 (95% CI, 0.49 to 1.54). Meta-analysis of the 2 rate ratios from each region resulted in a crude mortality ratio of 1.55 (95% CI, 1.22 to 1.96) and an adjusted mortality ratio of 1.11 (95% CI, 0.84 to 1.47). CONCLUSION:The presence of diabetes was not strongly associated with in-hospital COVID-19 mortality independent of illness severity and other comorbidities.

Neutralization of Omicron subvariants by different bivalent vaccines have not been well evaluated. This study characterized neutralization against Omicron subvariants in 98 individuals receiving dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P=0.48), BA.1 (P=0.21), BA.5 (P=0.07), BQ.1.1 (P=0.10), nor XBB.1.5 (P=0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. Given that both BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induced similar neutralization against all Omicron subvariants, this suggests that bivalent vaccines confer protection even when they are antigenically divergent from the circulating variant.

Abstract Background The spread of carbapenemase-producing Enterobacterales (CPE) is global threat. Numerous outbreaks of CPE have been reported during the COVID-19 pandemic. We describe the impact of of the SARS-CoV-2 pandemic on the emergence of CPE in south-central Ontario, Canada. Incidence of clinical isolates of CPE and isolates with different CPE genes in Toronto/Peel region, 2017–2021. The upper panel shows the incidence of patients with clinical isolates of CPE by year and quarter from q4 2007 to q1 2022. The lower panel shows the incidence of patients with clinical isolates with different carbapenemase genes by fiscal year during the same period. Methods TIBDN has performed population-based surveillance for CPE in Toronto/Peel region (pop 4.5M) from first identified isolate in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for identification of CPE. Hospital charts are reviewed and patients/physicians interviewed. Population data are obtained from Statistics Canada. Results From 10/2007 to 3/31/2022, 1367 persons colonized or infected with CPE were identified. Their median age was 68.7yrs (IQR 54–78yrs); 761 (56%) were male. 772 (56%) were colonized when first identified; 115 (8.4%) were bacteremic at identification or subsequently developed bacteremia. The most common organisms were E. coli (651, 48%), K. pneumoniae (436, 32%), Enterobacter spp. (146, 11%), Citrobacter spp (62, 5%); the most common genes were NDM±OXA-48 (722, 53%), OXA-48-like (341, 25%), KPC (225, 16%), VIM (44, 3%). The incidence of CPE infections increased steadily until 3/2020 then declined by 61% and remained stable until 3/2022 (Figure, upper panel). The decline was greater for E. coli (56% decrease), K. pneumoniae (62%) than for Enterobacter spp. (30%) and other species (19%). It occurred in all genes in 2020; however, KPC containing organisms increased again in 2021 (Figure, lower panel). Conclusion The advent of the COVID-19 pandemic was associated with an immediate, substantial decline in the incidence of patients with CPE in our population area. This decline occurred in both isolates with genes usually occurring in cases imported from other countries, and in those usually occurring in cases associated with transmission within Canadian hospitals. Decreased travel and enhanced infection prevention and control in hospitals may both have contributed to reductions in CPE during the pandemic. Disclosures All Authors: No reported disclosures.

Abstract Background There is wide variation in mortality among patients hospitalized with COVID‐19. Whether this is related to patient or hospital factors is unknown. Objective To compare the risk of mortality for patients hospitalized with COVID‐19 and to determine whether the majority of that variation was explained by differences in patient characteristics across sites. Design, Setting, and Participants An international multicenter cohort study of hospitalized adults with laboratory‐confirmed COVID‐19 enrolled from 10 hospitals in Ontario, Canada and 8 hospitals in Copenhagen, Denmark between January 1, 2020 and November 11, 2020. Main Outcomes and Measures Inpatient mortality. We used a multivariable multilevel regression model to compare the in‐hospital mortality risk across hospitals and quantify the variation attributable to patient‐level factors. Results There were 1364 adults hospitalized with COVID‐19 in Ontario (n = 1149) and in Denmark (n = 215). In Ontario, the absolute risk of in‐hospital mortality ranged from 12.0% to 39.8% across hospitals. Ninety‐eight percent of the variation in mortality in Ontario was explained by differences in the characteristics of the patients. In Denmark, the absolute risk of inpatients ranged from 13.8% to 20.6%. One hundred percent of the variation in mortality in Denmark was explained by differences in the characteristics of the inpatients. Conclusion There was wide variation in inpatient COVID‐19 mortality across hospitals, which was largely explained by patient‐level factors, such as age and severity of presenting illness. However, hospital‐level factors that could have affected care, including resource availability and capacity, were not taken into account. These findings highlight potential limitations in comparing crude mortality rates across hospitals for the purposes of reporting on the quality of care.

Objectives: SARS-CoV-2 shedding has changed as new variants have emerged. It is important to understand the trajectory of PCR positivity due to Omicron in vaccinated populations. Methods: Double- or triple-vaccinated adult household contacts of individuals with COVID-19 self-collected oral-nasal swabs for 14 days. A hierarchical linear model estimated viral load trajectories and an exploratory logistic regression model assessed for factors associated with viral detection before symptom onset. Results: Forty-one participants developed COVID-19 with 37 (90%) symptomatic. Viral load peaked 3 days after symptom onset at a median concentration of 8.83 log(10) copies/milliliter (range 5.95-10.32) and the mean difference between participants with two or three COVID-19 vaccine doses was 0.02 log(10) copies/milliliter (95% CI -0.13 to 0.16). PCR positivity began with a range of 4 days prior to 3 days after symptom onset and was positive on the day of symptom onset in 76% (28/37). SARS-CoV-2 detection on the day of symptom onset was less likely among those with 2 vaccine doses (OR 0.13, 95%CI 0.02-0.79). 68% (25/37) of infected participants had detectable SARS-CoV-2 with Ct<30 at 7 days after symptom onset. Conclusions: Peak viral load and duration of PCR positivity were similar in participants with COVID-19 after two versus three COVID-19 vaccine doses. Onset of viral detection relative to symptom onset was variable. (c) 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Among outpatients with COVID-19 due to the Delta variant who did and did not receive two vaccine doses at 7 days post symptom onset there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI -4.68-3.50; p=0.77) with SARS-CoV-2 cultured from 7% (2/28) and 4% (1/26), respectively.

BackgroundPeriprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty (TJA). Rifampin is an antibiotic with the ability to penetrate bacterial biofilms, and thus has been considered as a potentially important adjunct in the prevention and treatment of PJI. The aim of this systematic review is to evaluate and summarize the use of rifampin in TJA, particularly in the context of PJI.MethodsA literature search of all relevant electronic databases was performed. All comparative studies assessing the use of rifampin in the context of TJA were included. Descriptive data are reported, and a meta-analysis was performed using all studies which compared the addition of rifampin to standard care in treating PJI.ResultsA total of 33 studies met inclusion criteria. A meta-analysis of 22 studies comparing the addition of rifampin to standard care for treating PJI found a significant reduction in failure rates (26.0% vs 35.9%; odds ratio 0.61, 95% confidence interval 0.43-0.86). The protective effect of rifampin was maintained in studies which included exchange arthroplasty as a treatment strategy, but not in studies only using an implant retention strategy. Among studies reporting adverse events of rifampin, there was a 20.5% adverse event rate.ConclusionOverall, rifampin appears to confer a protective effect against treatment failure following PJI. This treatment effect is particularly pronounced in the context of exchange arthroplasty. Further high-level evidence is needed to clarify the exact indications and doses of rifampin which can most effectively act as an adjunct in the treatment of PJI.Level of evidenceLevel III, Systematic Review and Meta-Analysis of Level I-III Studies.

Background: Treatment outcomes in studies on prosthetic joint infection are generally assessed using a dichotomous outcome relating to treatment success or failure. These outcome measures neither include patient-centred outcome measures including joint function and quality of life, nor do they account for adverse effects of treatment. A desirability of outcome ranking (DOOR) measure can include these factors and has previously been proposed and validated for other serious infections. We aimed to develop a novel DOOR for prosthetic joint infections (PJIs). Methods: The Delphi method was used to develop a DOOR for PJI research. An international working group of 18 clinicians (orthopaedic surgeons and infectious disease specialists) completed the Delphi process. The final DOOR comprised the dimensions established to be most important by consensus with >75 % of participant agreement. Results: The consensus DOOR comprised four main dimensions. The primary dimension was patient-reported joint function. The secondary dimensions were infection cure and mortality. The final dimension of quality of life was selected as a tie-breaker. Discussion: A desirability of outcome ranking for periprosthetic joint infection has been proposed. It focuses on patient-centric outcome measures of joint function, cure and quality of life. This DOOR provides a multidimensional assessment to comprehensively rank outcomes when comparing treatments for prosthetic joint infection.