Risk of hospital admission and death from first-ever SARS-CoV-2 infection by age group during the Delta and Omicron periods in British Columbia, Canada.

BACKGROUND: Population-based cross-sectional serosurveys within the Lower Mainland, British Columbia, Canada, showed about 10%, 40% and 60% of residents were infected with SARS-CoV-2 by the sixth (September 2021), seventh (March 2022) and eighth (July 2022) serosurveys. We conducted the ninth (December 2022) and tenth (July 2023) serosurveys and sought to assess risk of severe outcomes from a first-ever SARS-CoV-2 infection during intersurvey periods. METHODS: Using increments in cumulative infection-induced seroprevalence, population census, discharge abstract and vital statistics data sets, we estimated infection hospitalization and fatality ratios (IHRs and IFRs) by age and sex for the sixth to seventh (Delta/Omicron-BA.1), seventh to eighth (Omicron-BA.2/BA.5) and eighth to ninth (Omicron-BA.5/BQ.1) intersurvey periods. As derived, IHR and IFR estimates represent the risk of severe outcome from a first-ever SARS-CoV-2 infection acquired during the specified intersurvey period. RESULTS: The cumulative infection-induced seroprevalence was 74% by December 2022 and 79% by July 2023, exceeding 80% among adults younger than 50 years but remaining less than 60% among those aged 80 years and older. Period-specific IHR and IFR estimates were consistently less than 0.3% and 0.1% overall. By age group, IHR and IFR estimates were less than 1.0% and up to 0.1%, respectively, except among adults aged 70-79 years during the sixth to seventh intersurvey period (IHR 3.3% and IFR 1.0%) and among those aged 80 years and older during all periods (IHR 4.7%, 2.2% and 3.5%; IFR 3.3%, 0.6% and 1.3% during the sixth to seventh, seventh to eighth and eighth to ninth periods, respectively). The risk of severe outcome followed a J-shaped age pattern. During the eighth to ninth period, we estimated about 1 hospital admission for COVID-19 per 300 newly infected children younger than 5 years versus about 1 per 30 newly infected adults aged 80 years and older, with no deaths from COVID-19 among children but about 1 death per 80 newly infected adults aged 80 years and older during that period. INTERPRETATION: By July 2023, we estimated about 80% of residents in the Lower Mainland, BC, had been infected with SARS-CoV-2 overall, with low risk of hospital admission or death; about 40% of the oldest adults, however, remained uninfected and at highest risk of a severe outcome. First infections among older adults may still contribute substantial burden from COVID-19, reinforcing the need to continue to prioritize this age group for vaccination and to consider them in health care system planning.

Serial cross-sectional estimation of vaccine-and infection-induced SARS-CoV-2 seroprevalence in British Columbia, Canada.

BACKGROUND: The evolving proportion of the population considered immunologically naive versus primed for more efficient immune memory response to SARS-CoV-2 has implications for risk assessment. We sought to chronicle vaccine- and infection-induced seroprevalence across the first 7 waves of the COVID-19 pandemic in British Columbia, Canada. METHODS: During 8 cross-sectional serosurveys conducted between March 2020 and August 2022, we obtained anonymized residual sera from children and adults who attended an outpatient laboratory network in the Lower Mainland (Greater Vancouver and Fraser Valley). We used at least 3 immunoassays per serosurvey to detect SARS-CoV-2 spike and nucleocapsid antibodies. We assessed any seroprevalence (vaccineor infection-induced, or both), defined by positivity on any 2 assays, and infection-induced seroprevalence, also defined by dual-assay positivity but requiring both antinucleocapsid and antispike detection. We used estimates of infection-induced seroprevalence to explore underascertainment of infections by surveillance case reports. RESULTS: By January 2021, we estimated that any seroprevalence remained less than 5%, increasing with vaccine rollout to 56% by May-June 2021, 83% by September-October 2021 and 95% by March 2022. Infection-induced seroprevalence remained less than 15% through September-October 2021, increasing across Omicron waves to 42% by March 2022 and 61% by July-August 2022. By August 2022, 70%-80% of children younger than 20 years and 60%-70% of adults aged 20-59 years had been infected, but fewer than half of adults aged 60 years and older had been infected. Compared with estimates of infection-induced seroprevalence, surveillance case reports underestimated infections 12-fold between September 2021 and March 2022 and 92-fold between March 2022 and August 2022. INTERPRETATION: By August 2022, most children and adults younger than 60 years had evidence of both SARS-CoV-2 vaccination and infection. As previous evidence suggests that a history of both exposures may induce stronger, more durable hybrid immunity than either exposure alone, older adults - who have the lowest infection rates but highest risk of severe outcomes - continue to warrant prioritized vaccination.

Age-Associated Seroprevalence of Coronavirus Antibodies: Population-Based Serosurveys in 2013 and 2020, British Columbia, Canada.

Background: Older adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age. Methods: To assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets. Results: Samples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally. Conclusion: Most people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.

Appropriateness of Outpatient Antibiotic Use in Seniors across Two Canadian Provinces.

Antimicrobials are among the most prescribed medications in Canada, with over 90% of antibiotics prescribed in outpatient settings. Seniors prescribed antimicrobials are particularly vulnerable to adverse drug events and antimicrobial resistance. The extent of inappropriate antibiotic prescribing in outpatient Canadian medical practice, and the potential long-term trends in this practice, are unknown. This study is the first in Canada to examine prescribing quality across two large-scale provincial healthcare systems to compare both quantity and quality of outpatient antibiotic use in seniors. Population-based analyses using administrative health databases were conducted in British Columbia (BC) and Ontario (ON), and all outpatient, oral antimicrobials dispensed to seniors (≥65 years) from 1 January 2000 to 31 December 2018 were identified. Antimicrobials were linked to an indication using a 3-tiered hierarchy. Tier 1 indications, which always require antibiotics, were given priority, followed by Tier 2 indications that sometimes require antibiotics, then Tier 3, which never require antibiotics. Prescription rates were calculated per 1000 population, and trends were examined overall, by drug class, and by patient demographics. Prescribing remained steady in both provinces, with 11,166,401 prescriptions dispensed overall in BC, and 27,656,014 overall in ON. BC prescribed at slightly elevated rates (range: 790 to 930 per 1000 residents), in comparison to ON (range: 745 to 785 per 1000 residents), throughout the study period. For both provinces, a Tier 3 diagnosis was the most common reason for antibiotic use, accounting for 50% of all indication-associated antibiotic prescribing. Although Tier 3 indications remained the most prescribed-for diagnoses throughout the study period, a declining trend over time is encouraging, with much room for improvement remaining. Elevated prescribing to seniors continues across Canadian outpatient settings, and prescribing quality is of high concern, with 50% of all antimicrobials prescribed inappropriately for common infections that do not require antimicrobials.

Outpatient antibiotic use in British Columbia, Canada: reviewing major trends since 2000.

BACKGROUND: With 90% of all antibiotics in Canada being used in the community setting, tracking outpatient prescribing is integral to mitigate the issue of antimicrobial resistance. In 2005, a provincial programme was launched in British Columbia (BC) to disseminate information regarding the judicious use of antibiotics. These efforts include educational campaigns, updated practitioner guidelines and academic detailing. The impact of provincial stewardship on community prescribing requires ongoing evaluation. OBJECTIVES: This study examines outpatient prescribing to quantify rates of antibiotic use, evaluate major trends over time and identify new targets for stewardship. METHODS: A retrospective cohort design using population-level data. RESULTS: This study included over 3.5 million unique individuals with a total of 51 367 938 oral antibiotic prescriptions dispensed over a 19 year period (2000-18). Overall antibiotic utilization decreased by 23% over the course of the study period. This trend in the reduction of antibiotic prescription was observed across all major antibiotic classes, apart from the class of other antibacterials, which was mostly related to use of nitrofurantoin. The largest magnitudes of decreased prescribing were observed in the paediatric population. Prescribing across two distinct eras of provincial stewardship reaffirmed preliminary findings of programme efficacy, when compared with pre-stewardship levels of antibiotic use. CONCLUSIONS: Outpatient prescribing in BC is decreasing overall, and this study confirms an association between provincial stewardship interventions and improvements in antibiotic use. Pronounced declines in paediatric populations are promising, and further research is underway to examine prescribing quality.

Comparison of three phenotypic techniques for detection of methicillin resistance in Staphylococcus spp. reveals a species-dependent performance.

OBJECTIVES: To evaluate the usefulness of the cefoxitin screen in Vitek 2 Gram-positive panels for recognizing methicillin-resistant strains of staphylococci. METHODS: Seven hundred and ninety-nine non-duplicate isolates of Staphylococcus aureus and coagulase-negative strains were included in the study. Methicillin resistance was measured using PCR for the mecA gene, the CLSI cefoxitin disc diffusion method, the Vitek 2 cefoxitin screen and the Vitek 2 oxacillin susceptibility test. RESULTS: Compared with the molecular detection of methicillin resistance the overall sensitivities and specificities of the phenotypic tests for cefoxitin disc diffusion were 94.9% and 97.0%, for Vitek 2 cefoxitin screen were 94.6% and 93.5% and for Vitek 2 oxacillin susceptibility test were 93.8% and 77.9%. The cephamycin tests (cefoxitin disc diffusion and Vitek 2 screen) were not able to identify mecA-positive strains of Staphylococcus simulans. In addition, the performance of the Vitek 2 system was poor against Staphylococcus cohnii subspecies, Staphylococcus hominis hominis and Staphylococcus saprophyticus. CONCLUSIONS: Overall, the performance of the Vitek 2 system for differentiating mecA-positive staphylococci was comparable to PCR and the CLSI disc diffusion method; however, performance was species-dependent. Thus, before accepting the results produced by Vitek 2, species identification may be required.

Evaluation of a new chromogenic medium for the detection of methicillin-resistant Staphylococcus aureus carriage on nasal and perianal specimens.

A new chromogenic medium, denim blue (DB), was compared with methicillin-resistant Staphylococcus aureus (MRSA) Select (MRSAS) for detection of MRSA from surveillance specimens. On DB, MRSA colonies are larger (0.57-0.8 versus 0.45-0.6 mm at 18 and 24 h, respectively). Despite this, sensitivities of DB were 77% and 96% at 18 and 24 h, respectively, and those of MRSAS were 63% and 97.5%. Specificities were significantly higher for MRSAS than DB. The study demonstrates that DB and MRSA are equal for the detection of MRSA from surveillance specimens provided the plates are read after 24 h of incubation. Positive predictive values of both media were less than 95% requiring confirmation of MRSA, by another method, from all new patients.

Performance of TechLab C. DIFF QUIK CHEK and TechLab C. DIFFICILE TOX A/B II for the detection of Clostridium difficile in stool samples.

UNLABELLED: Two membrane-bound enzyme immunoassays by TechLab, Blacksburg, VA, were evaluated and compared with the Triage Micro C. difficile Panel (Biosite Diagnostics, San Diego, CA), with culture, and with cytotoxic assay. The TechLab panels were C. DIFF QUIK CHEK (QC-GDH) and C. DIFFICILE TOX A/B II (QC-toxinA/B), which detect glutamate dehydrogenase (GDH) and Clostridium difficile toxins A and B, respectively. The Triage Panel detects GDH (TR-GDH) and toxin A (TR-toxinA). METHODS: Stool samples were inoculated onto CCFA plates (Q-Labs, Quebec, Canada) after alcohol shock, and suspected colonies were identified by the MicroScreen C. difficile latex slide agglutination test (Microgen Bioproducts, Surrey, UK). TR-GDH, TR-toxinA, QC-GDH, and QC-toxinA/B tests were performed according to the manufacturers' instructions on all the samples. Samples positive for GDH or culture but negative for TR-toxinA and QC-toxinA/B were further tested by cytotoxin assay (CTA). CTA was also performed on samples that caused blackening of the Triage Micro C. difficile Panel. RESULTS: A total of 313 of 401 stool samples were negative for GDH and toxins (78%). Eighty-eight samples were positive either for GDH or culture or both. Thirteen of these could not be evaluated for C. difficile-associated diarrhea (CDAD) because CTA test was not performed. Toxin/s was detected at least by one method in 46 (11.8%) of 388 samples that were positive for culture or GDH and were considered diagnostic of CDAD. The QC-GDH was more sensitive than culture and TR-GDH for the detection of C. difficile. However, in 18GDH-positive samples positive for either of the Triage or TechLab immunoassays, the culture remained negative. Ten (2%) results of the Triage immunoassays could not be evaluated because of discoloration of the panels. QC-GDH (93.5%) was more sensitive for detecting the presence of toxin-producing C. difficile than TR-GDH (79.5%). TR-toxinA was more specific for detecting the presence of toxin-producing C. difficile than QC-toxinA/B (100% and 96.9%, respectively). CONCLUSIONS: The GDH tests had a faster turnaround time than the traditional culture methods. QC-GDH was most sensitive for the detection C. difficile-positive stools and was easy to use.

Risk factors for posterior vitreous detachment: a case-control study.

PURPOSE: To identify possible risk factors for the development of posterior vitreous detachment (PVD). DESIGN: Retrospective case-control study. METHODS: A total of 138 cases with PVD and 114 age-matched controls were accrued from two different sites. Demographic, medical, ocular, and lifestyle data were obtained through chart review, questionnaires, and clinical examination. A 108-item semiquantitative food frequency questionnaire was also used to estimate macro- and micronutrient intake. Univariate and multivariate regression analyses were employed to identify variables significantly associated with the main outcome measure of PVD. Subgroup analysis of gender-specific variables was performed. RESULTS: Among all patients, multivariate regression analysis demonstrated female gender (odds ratio [OR] = 2.01, P = .016), myopic refraction (OR = 4.32, P < .0005), and higher intake of vitamin B6 (OR = 2.61, P = .001) to be associated with PVD after controlling for age. In the subgroup analysis of women, menopause (OR = 18.2, P < .0005), myopic refraction (OR = 3.42, P = .01), and higher intake of vitamin B6 (OR = 3.92, P = .005) were associated with PVD. Specifically, there was a significant association between vitamin B6 and PVD amongst premenopausal women but not amongst postmenopausal women. CONCLUSIONS: An association between PVD and menopause has not been documented previously. We suspect that high estrogen levels seen in premenopausal women may be protective against PVD and that hormonal changes associated with menopause may lead to changes in the vitreous, predisposing to PVD. Higher levels of intake of vitamin B6 were also associated with the development of PVD in premenopausal women possibly through an anti-estrogen effect. These findings should be investigated further with prospective studies.