Severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Pregnancy in Ontario: A Matched Cohort Analysis.

BACKGROUND: Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination. METHODS: We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10-49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression. RESULTS: Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86-6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29-13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity, .004). CONCLUSIONS: Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women.

Relative Virulence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Vaccinated and Unvaccinated Individuals Hospitalized With SARS-CoV-2.

BACKGROUND: The rapid development of safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a singular scientific achievement. Confounding due to health-seeking behaviors, circulating variants, and differential testing by vaccination status may bias analyses toward an apparent increase in infection severity following vaccination. METHODS: We used data from the Ontario, Canada, Case and Contact Management Database and a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Vaccinated individuals were matched to up to 5 unvaccinated individuals based on test date. Risk of intensive care unit (ICU) admission and death were evaluated using conditional logistic regression. RESULTS: In 20 064 individuals (3353 vaccinated and 16 711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between 1 January 2021 and 5 January 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose-response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio [aOR] per additional dose for ICU admission, 0.66; 95% confidence interval [CI], .62 to .71; aOR for death, 0.78; 95% CI, .72 to .84). CONCLUSIONS: We identified decreased virulence of SARS-CoV-2 infections in vaccinated individuals, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel variants of concern, vaccines remain an important tool for reduction of ICU admission and mortality.

Age-Specific Changes in Virulence Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern.

BACKGROUND: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown. METHODS: We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends. RESULTS: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. CONCLUSIONS: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.

Impact of population mixing between vaccinated and unvaccinated subpopulations on infectious disease dynamics: implications for SARS-CoV-2 transmission.

BACKGROUND: The speed of vaccine development has been a singular achievement during the COVID-19 pandemic, although uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. We sought to explore the impact of mixing of vaccinated and unvaccinated populations on risk of SARS-CoV-2 infection among vaccinated people. METHODS: We constructed a simple susceptible-infectious-recovered compartmental model of a respiratory infectious disease with 2 connected subpopulations: people who were vaccinated and those who were unvaccinated. We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to complete like-with-like mixing (complete assortativity), in which people have contact exclusively with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup and in the population as a whole. RESULTS: We found that the risk of infection was markedly higher among unvaccinated people than among vaccinated people under all mixing assumptions. The contact-adjusted contribution of unvaccinated people to infection risk was disproportionate, with unvaccinated people contributing to infections among those who were vaccinated at a rate higher than would have been expected based on contact numbers alone. We found that as like-with-like mixing increased, attack rates among vaccinated people decreased from 15% to 10% (and increased from 62% to 79% among unvaccinated people), but the contact-adjusted contribution to risk among vaccinated people derived from contact with unvaccinated people increased. INTERPRETATION: Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to people who are unvaccinated, their choices affect risk of viral infection among those who are vaccinated in a manner that is disproportionate to the portion of unvaccinated people in the population.

COVID-19 Case Age Distribution: Correction for Differential Testing by Age.

BACKGROUND: Despite expected initial universal susceptibility to a novel pandemic pathogen like SARS-CoV-2, the pandemic has been characterized by higher observed incidence in older persons and lower incidence in children and adolescents. OBJECTIVE: To determine whether differential testing by age group explains observed variation in incidence. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Persons diagnosed with SARS-CoV-2 and those tested for SARS-CoV-2. MEASUREMENTS: Test volumes from the Ontario Laboratories Information System, number of laboratory-confirmed SARS-CoV-2 cases from the Integrated Public Health Information System, and population figures from Statistics Canada. Demographic and temporal patterns in incidence, testing rates, and test positivity were explored using negative binomial regression models and standardization. Sources of variation in standardized ratios were identified and test-adjusted standardized infection ratios (SIRs) were estimated by metaregression. RESULTS: Observed disease incidence and testing rates were highest in the oldest age group and markedly lower in those younger than 20 years; no differences in incidence were seen by sex. After adjustment for testing frequency, SIRs were lowest in children and in adults aged 70 years or older and markedly higher in adolescents and in males aged 20 to 49 years compared with the overall population. Test-adjusted SIRs were highly correlated with standardized positivity ratios (Pearson correlation coefficient, 0.87 [95% CI, 0.68 to 0.95]; P < 0.001) and provided a case identification fraction similar to that estimated with serologic testing (26.7% vs. 17.2%). LIMITATIONS: The novel methodology requires external validation. Case and testing data were not linkable at the individual level. CONCLUSION: Adjustment for testing frequency provides a different picture of SARS-CoV-2 infection risk by age, suggesting that younger males are an underrecognized group at high risk for SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Involuntary isolation: interpreting mental health legislation during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic poses new and unprecedented challenges to the interpretation of mental health law. The authors present pragmatic and ethical considerations in the psychiatric safety assessment at the intersection of COVID-19 and severe mental illness.

Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.

BACKGROUND: Between February and June 2021, the initial wild-type strains of SARS-CoV-2 were supplanted in Ontario, Canada, by new variants of concern (VOCs), first those with the N501Y mutation (i.e., Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants) and then the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented, but knowledge about their virulence is limited. We used Ontario's COVID-19 case data to evaluate the virulence of these VOCs compared with non-VOC SARS-CoV-2 strains, as measured by risk of hospitalization, intensive care unit (ICU) admission and death. METHODS: We created a retrospective cohort of people in Ontario who tested positive for SARS-CoV-2 and were screened for VOCs, with dates of test report between Feb. 7 and June 27, 2021. We constructed mixed-effect logistic regression models with hospitalization, ICU admission and death as outcome variables. We adjusted models for age, sex, time, vaccination status, comorbidities and pregnancy status. We included health units as random intercepts. RESULTS: Our cohort included 212 326 people. Compared with non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (95% confidence interval [CI] 42%-63%) for hospitalization, 89% (95% CI 67%-117%) for ICU admission and 51% (95% CI 30%-78%) for death. Increased risk with the Delta variant was more pronounced at 108% (95% CI 78%-140%) for hospitalization, 235% (95% CI 160%-331%) for ICU admission and 133% (95% CI 54%-231%) for death. INTERPRETATION: The increasing virulence of SARS-CoV-2 VOCs will lead to a considerably larger, and more deadly, pandemic than would have occurred in the absence of the emergence of VOCs.

The effect of average temperature on suicide rates in five urban California counties, 1999-⁠2019: an ecological time series analysis.

BACKGROUND: Suicide is among the top 10 leading causes of premature morality in the United States and its rates continue to increase. Thus, its prevention has become a salient public health responsibility. Risk factors of suicide transcend the individual and societal level as risk can increase based on climatic variables. The purpose of the present study is to evaluate the association between average temperature and suicide rates in the five most populous counties in California using mortality data from 1999 to 2019. METHODS: Monthly counts of death by suicide for the five counties of interest were obtained from CDC WONDER. Monthly average, maximum, and minimum temperature were obtained from nCLIMDIV for the same time period. We modelled the association of each temperature variable with suicide rate using negative binomial generalized additive models accounting for the county-specific annual trend and monthly seasonality. RESULTS: There were over 38,000 deaths by suicide in California's five most populous counties between 1999 and 2019. An increase in average temperature of 1 °C corresponded to a 0.82% increase in suicide rate (IRR = 1.0082 per °C; 95% CI = 1.0025-1.0140). Estimated coefficients for maximum temperature (IRR = 1.0069 per °C; 95% CI = 1.0021-1.0117) and minimum temperature (IRR = 1.0088 per °C; 95% CI = 1.0023-1.0153) were similar. CONCLUSION: This study adds to a growing body of evidence supporting a causal effect of elevated temperature on suicide. Further investigation into environmental causes of suicide, as well as the biological and societal contexts mediating these relationships, is critical for the development and implementation of new public health interventions to reduce the incidence of suicide, particularly in the face increasing temperatures due to climate change.

Quantifying contact patterns in response to COVID-19 public health measures in Canada.

BACKGROUND: A variety of public health measures have been implemented during the COVID-19 pandemic in Canada to reduce contact between individuals. The objective of this study was to provide empirical contact pattern data to evaluate the impact of public health measures, the degree to which social contacts rebounded to normal levels, as well as direct public health efforts toward age- and location-specific settings. METHODS: Four population-based cross-sectional surveys were administered to members of a paid panel representative of Canadian adults by age, gender, official language, and region of residence during May (Survey 1), July (Survey 2), September (Survey 3), and December (Survey 4) 2020. A total of 4981 (Survey 1), 2493 (Survey 2), 2495 (Survey 3), and 2491 (Survey 4) respondents provided information about the age and setting for each direct contact made in a 24-h period. Contact matrices were constructed and contacts for those under the age of 18 years imputed. The next generation matrix approach was used to estimate the reproduction number (Rt) for each survey. Respondents with children under 18 years estimated the number of contacts their children made in school and extracurricular settings. RESULTS: Estimated Rt values were 0.49 (95% CI: 0.29-0.69) for May, 0.48 (95% CI: 0.29-0.68) for July, 1.06 (95% CI: 0.63-1.52) for September, and 0.81 (0.47-1.17) for December. The highest proportion of reported contacts occurred within the home (51.3% in May), in 'other' locations (49.2% in July) and at work (66.3 and 65.4% in September and December). Respondents with children reported an average of 22.7 (95% CI: 21.1-24.3) (September) and 19.0 (95% CI 17.7-20.4) (December) contacts at school per day per child in attendance. CONCLUSION: The skewed distribution of reported contacts toward workplace settings in September and December combined with the number of reported school-related contacts suggest that these settings represent important opportunities for transmission emphasizing the need to support and ensure infection control procedures in both workplaces and schools.

Mathematical modelling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada.

BACKGROUND: Physical-distancing interventions are being used in Canada to slow the spread of severe acute respiratory syndrome coronavirus 2, but it is not clear how effective they will be. We evaluated how different nonpharmaceutical interventions could be used to control the coronavirus disease 2019 (COVID-19) pandemic and reduce the burden on the health care system. METHODS: We used an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada. We compared a base case with limited testing, isolation and quarantine to scenarios with the following: enhanced case finding, restrictive physical-distancing measures, or a combination of enhanced case finding and less restrictive physical distancing. Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected occupancy of intensive care unit (ICU) beds. We present medians and credible intervals from 100 replicates per scenario using a 2-year time horizon. RESULTS: We estimated that 56% (95% credible interval 42%-63%) of the Ontario population would be infected over the course of the epidemic in the base case. At the epidemic peak, we projected 107 000 (95% credible interval 60 760-149 000) cases in hospital (non-ICU) and 55 500 (95% credible interval 32 700-75 200) cases in ICU. For fixed-duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive physical distancing estimated to have the greatest effect. Longer duration interventions were more effective. Dynamic interventions were projected to reduce the proportion of the population infected at the end of the 2-year period and could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity. INTERPRETATION: Without substantial physical distancing or a combination of moderate physical distancing with enhanced case finding, we project that ICU resources would be overwhelmed. Dynamic physical distancing could maintain health-system capacity and also allow periodic psychological and economic respite for populations.

Impact of climate and public health interventions on the COVID-19 pandemic: a prospective cohort study.

BACKGROUND: It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). RESULTS: In univariate analyses, there were no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85-0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85-0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53-0.79), school closures (RRR 0.63, 95% CI 0.52-0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45-0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. INTERPRETATION: Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

The Relative Impact of Community and Hospital Antibiotic Use on the Selection of Extended-spectrum Beta-lactamase-producing Escherichia coli.

Antibiotic stewardship programs have traditionally focused on reducing hospital antibiotic use. However, reducing community antibiotic prescribing could have substantial impacts in both hospital and community settings. We developed a deterministic model of transmission of extended-spectrum beta-lactamase-producing Escherichia coli in both the community and hospitals. We fit the model to existing, national-level antibiotic use and resistance prevalence data from Sweden. Across a range of conditions, a given relative change in antibiotic use in the community had a greater impact on resistance prevalence in both the community and hospitals than an equivalent relative change in hospital use. However, on a per prescription basis, changes in antibiotic use in hospitals had the greatest impact. The magnitude of changes in prevalence were modest, even with large changes in antimicrobial use. These data support the expansion of stewardship programs/interventions beyond the walls of hospitals, but also suggest that such efforts would benefit hospitals themselves.

Effects of large-scale oceanic phenomena on non-cholera vibriosis incidence in the United States: implications for climate change.

Non-cholera Vibrio (NCV) species are important causes of disease. These pathogens are thermophilic and climate change could increase the risk of NCV infection. The El Niño Southern Oscillation (ENSO) is a 'natural experiment' that may presage ocean warming effects on disease incidence. In order to evaluate possible climatic contributions to observed increases in NCV infection, we obtained NCV case counts for the United States from publicly available surveillance data. Trends and impacts of large-scale oceanic phenomena, including ENSO, were evaluated using negative binomial and distributed non-linear lag models (DNLM). Associations between latitude and changing risk were evaluated with meta-regression. Trend models demonstrated expected seasonality (P < 0.001) and a 7% (6.1%-8.1%) annual increase in incidence from 1999 to 2014. DNLM demonstrated increased vibriosis risk following ENSO conditions over the subsequent 12 months (relative risk 1.940, 95% confidence interval (CI) 1.298-2.901). The 'relative-relative risk' (RRR) of annual disease incidence increased with latitude (RRR per 10° increase 1.066, 95% CI 1.027-1.107). We conclude that NCV risk in the United States is impacted by ocean warming, which is likely to intensify with climate change, increasing NCV risk in vulnerable populations.

Impact of El Niño Southern Oscillation on infectious disease hospitalization risk in the United States.

Although the global climate is changing at an unprecedented rate, links between weather and infectious disease have received little attention in high income countries. The "El Niño Southern Oscillation" (ENSO) occurs irregularly and is associated with changing temperature and precipitation patterns. We studied the impact of ENSO on infectious diseases in four census regions in the United States. We evaluated infectious diseases requiring hospitalization using the US National Hospital Discharge Survey (1970-2010) and five disease groupings that may undergo epidemiological shifts with changing climate: (i) vector-borne diseases, (ii) pneumonia and influenza, (iii) enteric disease, (iv) zoonotic bacterial disease, and (v) fungal disease. ENSO exposure was based on the Multivariate ENSO Index. Distributed lag models, with adjustment for seasonal oscillation and long-term trends, were used to evaluate the impact of ENSO on disease incidence over lags of up to 12 mo. ENSO was associated more with vector-borne disease [relative risk (RR) 2.96, 95% confidence interval (CI) 1.03-8.48] and less with enteric disease (0.73, 95% CI 0.62-0.87) in the Western region; the increase in vector-borne disease was attributable to increased risk of rickettsioses and tick-borne infectious diseases. By contrast, ENSO was associated with more enteric disease in non-Western regions (RR 1.12, 95% CI 1.02-1.15). The periodic nature of ENSO may make it a useful natural experiment for evaluation of the impact of climatic shifts on infectious disease risk. The impact of ENSO suggests that warmer temperatures and extreme variation in precipitation events influence risks of vector-borne and enteric disease in the United States.

Can enhanced screening of men with a history of prior syphilis infection stem the epidemic in men who have sex with men? A mathematical modelling study.

OBJECTIVES: The aim of this study is to determine the transmission impact of using prior syphilis infection to guide a focused syphilis screening intervention among men who have sex with men (MSM). METHODS: We parameterised a deterministic model of syphilis transmission in MSM to reflect the 2011-2015 syphilis outbreak in Winnipeg, Canada. Enhanced screening of 75% of men with prior syphilis every 3 months (A) was compared with distributing equivalent number tests to all MSM (B) or those with the highest partner number (C). We compared early syphilis incidence, diagnoses and prevalence after 10 years, relative to a base case of 30% of MSM screened annually. RESULTS: Strategy A was expected to avert 52% of incident infections, 44% of diagnosed cases and reduce early syphilis prevalence by 89%. Strategy B had the least impact. Strategy C was most effective, averting 59% of incident cases. When screening frequency was semiannual or annual, strategy A was the most effective. CONCLUSIONS: Enhanced screening of MSM with prior syphilis may efficiently reduce transmission, especially when identification of high-risk men via self-reported partner numbers or high-frequency screening is difficult to achieve.

Second-pandemic strain of Vibrio cholerae from the Philadelphia cholera outbreak of 1849.

In the 19th century, there were several major cholera pandemics in the Indian subcontinent, Europe, and North America. The causes of these outbreaks and the genomic strain identities remain a mystery. We used targeted high-throughput sequencing to reconstruct the Vibrio cholerae genome from the preserved intestine of a victim of the 1849 cholera outbreak in Philadelphia, part of the second cholera pandemic. This O1 biotype strain has 95 to 97% similarity with the classical O395 genome, differing by 203 single-nucleotide polymorphisms (SNPs), lacking three genomic islands, and probably having one or more tandem cholera toxin prophage (CTX) arrays, which potentially affected its virulence. This result highlights archived medical remains as a potential resource for investigations into the genomic origins of past pandemics.