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BackgroundOur objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. MethodsWe conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. ResultsThe final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. InterpretationNirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.
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ImportanceResident crowding in nursing homes is associated with larger SARS-CoV-2 outbreaks. However, this association has not been previously documented for non-SARS-CoV-2 respiratory infections. ObjectiveWe sought to measure the association between nursing home crowding and respiratory infections in Ontario nursing homes prior to the COVID-19 pandemic. Design, Setting, and ParticipantsWe conducted a retrospective cohort study of nursing home residents in Ontario, Canada over a five-year period prior to the COVID-19 pandemic, between September 2014 and August 2019. ExposureUsing administrative data, we estimated the crowding index equal to the mean number of residents per bedroom and bathroom (residents / [0.5*bedrooms+0.5*bathrooms]). OutcomesThe incidence of outbreak-associated infections and mortality per 100 nursing home residents per year. We also examined infection and mortality outcomes for outbreaks due to 7 specific pathogens: coronaviruses (OC43, 229E, NL63, HKU1), influenza A, influenza B, human metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus/enterovirus. ResultsThere was one or more respiratory outbreak in 93.9% (588/626) nursing homes in Ontario. There were 4,921 outbreaks involving 64,829 cases of respiratory infection, and 1,969 deaths. Outbreaks attributable to a single identified pathogen were principally caused by influenza A (29%), rhinovirus (11.7%), influenza B (8.1%), and respiratory syncytial virus (6.1%). Among homes, 42.7% (251/588) homes had a high crowding index ([≥] 2.0). After adjustment, more crowded homes had higher outbreak-associated respiratory infection incidence (aRR 1.89; 95% 1.64-2.18) and mortality incidence (aRR 2.28; 95% 1.84-2.84). More crowded homes had higher adjusted estimates of the incidence of infection and mortality for each of the 7 respiratory pathogens examined. Conclusions and RelevanceResidents of crowded nursing homes experienced more respiratory-outbreak infections and mortality due to influenza and other non-SARS-CoV-2 respiratory pathogens. Decreasing crowding in nursing homes is an important patient safety target beyond the COVID-19 pandemic.
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BackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada. MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals. ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after [≥]240 days, but increased to 97% (95%CI, 96-98%) [≥]7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after [≥]180 days, but increased to 61% (95%CI, 56-65%) [≥]7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively). ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.
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SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax), and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection [≥]7 days after two doses was 89-92% against Alpha, 87% against Beta, 88% against Gamma, 82-89% against Beta/Gamma, and 87-95% against Delta across vaccine products. The corresponding estimates [≥]14 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults ([≥]60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.
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BackgroundThe emergence of SARS-CoV-2 variants associated with increased transmissibility are driving a 3rd global surge in COVID-19 incidence. There are currently few reliable estimates for the P.1 and B.1.351 lineages. We sought to compare the secondary attack rates of SARS-COV-2 mutations and variants in Canadas largest province of Ontario, using a previously validated household-based approach. MethodsWe identified individuals with confirmed SARS-CoV-2 infection in Ontarios provincial reportable disease surveillance system. Cases were grouped into households based on reported residential address. Index cases had the earliest of symptom onset in the household. Household secondary attack rate was defined as the percentage of household contacts identified as secondary cases within 1-14 days after the index case. ResultsWe identified 26,888 index household cases during the study period. Among these, 7,555 (28%) were wild-type, 17,058 (63%) were B.1.1.7, 1674 (6%) were B.1.351 or P.1, and 601 (2%) were non-VOC mutants (Table 1). The secondary attack rates, according to index case variant were as follows: 20.2% (wild-type), 25.1% (B.1.1.7), 27.2% (B.1.351 or P.1), and 23.3% (non-VOC mutants). In adjusted analyses, we found that B.1.1.7, B.1.351, and P.1 index cases had the highest transmissibility (presumptive B.1.1.7 ORadjusted=1.49, 95%CI 1.36, 1.64; presumptive B.1.351 or P.1 ORadjusted=1.60, 95%CI 1.37, 1.87). O_TBL View this table: org.highwire.dtl.DTLVardef@1f1a4e9org.highwire.dtl.DTLVardef@181f042org.highwire.dtl.DTLVardef@1c483fborg.highwire.dtl.DTLVardef@b4fba0org.highwire.dtl.DTLVardef@1f3d626_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSecondary attack rates of persons infected with SARS-CoV-2, March 1 to April 17. C_TABLECAPTION C_TBL DiscussionSubstantially higher transmissibility associated with variants will make control of SARS-CoV-2 more difficult, reinforcing the urgent need to increase vaccination rates globally.
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ObjectivesTo estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. DesignWe applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes. SettingOntario, Canada between 14 December 2020 and 19 April 2021. ParticipantsCommunity-dwelling adults aged [≥]16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. InterventionsPfizer-BioNTechs BNT162b2 or Modernas mRNA-1273 vaccine. Main outcome measuresLaboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection. ResultsAmong 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received [≥]1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection [≥]14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14-20 days after the first dose to 71% (95%CI, 63 to 78%) at 35-41 days. VE [≥]7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE [≥]14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14-20 days to 91% (95%CI, 73 to 97%) at [≥]35 days, whereas VE [≥]7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged [≥]70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants. ConclusionsTwo doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.
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BACKGROUNDAs a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. This study sought to determine whether there are differences in the odds of household transmission for younger children compared to older children. METHODSWe assembled a cohort of all individuals in Ontario, Canada with laboratory-confirmed SARS-CoV-2 infection between June 1 and December 31, 2020. The cohort was restricted to individuals residing in private households (N=132,232 cases in 89,191 households), identified through an address matching algorithm. Analysis focused on households in which the index case was aged <18 years. Logistic regression models were fit to estimate the association between age group of pediatric index cases (0-3, 4-8, 9-13, and 14-17 years) and odds of household transmission. RESULTSA total of 6,280 households had pediatric index cases, and 1,717 (27.3%) experienced secondary transmission. Children aged 0-3 years had the highest odds of household transmission compared to children aged 14-17 years (model adjusted for gender, month of disease onset, testing delay, and average family size: 1.43, 95% CI: 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2-14 days or 4-14 days after the index case, and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4-8 years and 9-13 years also had increased odds of transmission (4-8: 1.40, 95% CI: 1.18-1.67; 9-13: 1.13, 95% CI: 0.97-1.32). CONCLUSIONSThis study suggests that younger children are more likely to transmit SARS-CoV-2 infection compared to older children, and the highest odds of transmission was observed for children aged 0-3 years. Differential infectivity of pediatric age groups has implications for infection prevention controls within households, as well as schools/childcare, to minimize risk of household secondary transmission.
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ImportanceNursing home residents have been disproportionately impacted by the COVID-19 epidemic. Prevention recommendations have emphasized frequent testing of healthcare personnel and residents, but additional strategies are needed to protect nursing home residents. ObjectiveWe developed a reproducible index of nursing home crowding and determined whether crowding was associated with incidence of COVID-19 in the first months of the COVID-19 epidemic. Design, Setting, and ParticipantsPopulation-based retrospective cohort study of over 78,000 residents of 618 distinct nursing homes in Ontario, Canada from March 29 to May 20, 2020. ExposureThe nursing home crowding index equalled the average number of residents per bedroom and bathroom. OutcomesPrimary outcomes included the cumulative incidence of COVID-19 infection and mortality, per 100 residents; introduction of COVID-19 into a home ([≥]1 resident case) was a negative tracer. ResultsOf 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78,607 residents. A total of 5,218 residents (6.6%) developed COVID-19 infection, and 1,452 (1.8%) died with COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes: 4,496 (86%) of infections occurred in just 63 (10%) of homes. The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 (50%) homes had high crowding index ([≥]2). Incidence in high crowding index homes was 9.7%, versus 4.5% in low crowding index homes (p<0.001), while COVID-19 mortality was 2.7%, versus 1.3%. The likelihood of COVID-19 introduction did not differ (31.3% vs 30.2%, p=0.79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with increased risk of infection (RR=1.72, 95% Confidence Interval [CI]: 1.11-2.65) and mortality (RR=1.72, 95%CI: 1.03-2.86). Propensity score analysis yielded similar conclusions for infection (RR=2.06, 95%CI: 1.34-3.17) and mortality (RR=2.09, 95%CI: 1.30-3.38). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 988 (18.9%) infections of COVID-19 and 271 (18.7%) deaths. Conclusions and RelevanceCrowding was associated with higher incidence of COVID-19 infection and mortality. Reducing crowding in nursing homes could prevent future COVID-19 mortality.
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ImportanceProtecting healthcare workers (HCWs) from COVID-19 is a priority to maintain a safe and functioning healthcare system. The risk of transmitting COVID-19 to family members is a source of stress for many. ObjectiveTo describe and compare HCW and non-HCW COVID-19 cases in Ontario, Canada, as well as the frequency of COVID-19 among HCWs household members. Design, Setting, and ParticipantsUsing reportable disease data at Public Health Ontario which captures all COVID-19 cases in Ontario, Canada, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with COVID-19 as of 14 May 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. Exposures and OutcomesWe contrasted age, gender, comorbidities, clinical presentation (including asymptomatic and presymptomatic), exposure histories including nosocomial transmission, and clinical outcomes between HCWs and non-HCWs with confirmed COVID-19. ResultsThere were 4,230 (17.5%) HCW COVID-19 cases in Ontario, of whom 20.2% were nurses, 2.3% were physicians, and the remaining 77.4% other specialties. HCWs were more likely to be between 30-60 years of age and female. HCWs were more likely to present asymptomatically (8.1% versus 7.0%, p=0.010) or with atypical symptoms (17.8% versus 10.5%, p<0.001). The mortality among HCWs was 0.2% compared to 10.5% of non-HCWs. HCWs commonly had exposures to a confirmed case or outbreak (74.1%), however only 3.1% were confirmed to be nosocomial. The rate of new infections was 5.5 times higher in HCWs than non-HCWs, but mirrored the epidemic curve. We identified 391 (9.8%) probable secondary household transmissions and 143 (3.6%) acquisitions. Children < 19 years comprised 14.6% of secondary cases compared to only 4.2% of the primary cases. Conclusions and RelevanceHCWs represent a disproportionate number of COVID-19 cases in Ontario but with low confirmed numbers of nosocomial transmission. The data support substantial testing bias and under-ascertainment of general population cases. Protecting HCWs through appropriate personal protective equipment and physical distancing from colleagues is paramount. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the differences between healthcare workers and non-healthcare workers with COVID-19? FindingsIn this population-based cross-sectional study there were 4,230 healthcare workers comprising 17.5% of COVID-19 cases. Healthcare workers were diagnosed with COVID-19 at a rate 5.5 times higher than the general population with 0.8% of all healthcare workers, compared to 0.1% of non-healthcare workers. MeaningHigh healthcare worker COVID-19 burden highlights the importance of physical distancing from colleagues, appropriate personal protective equipment, as well as likely substantial testing bias and under-ascertainment of COVID-19 in the general population.
