ABSTRACT
ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes. ObjectiveTo evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality. Design, Setting, ParticipantsWe conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021). InterventionContrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) {+/-} transesophageal echocardiography (TEE) assessed for the presence of R-L shunts. Main Outcomes and MeasuresPrimary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt presence/absence with covariables. ResultsThe study enrolled 226 patients (182 COVID-19 vs. 42 non-COVID). Median age was 58 years (interquartile range [IQR]: 47-67) and APACHE II scores of 30 (IQR: 21-36). In COVID-19 patients, the incidence of R-L shunt was 31/182 patients (17.0%; intra-pulmonary: 61.3%; intra-cardiac: 38.7%) versus 10/44 (22.7%) non-COVID patients. No evidence of difference was detected between the COVID-19 and non-COVID-19 shunt rates (risk difference [RD]: -5.7%, 95% CI: -18.4-7.0, p=0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared to those without (54.8% vs 35.8%, RD: 19.0%, 95% CI 0.1-37.9, p=0.05). But this did not persist at 90-day mortality, nor after regression adjustments for age and illness severity. ConclusionsThere was no evidence of increased R-L shunt rates in COVID-19 compared to non-COVID controls. Right-to-left shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression. Key Points QuestionDoes right-to-left shunt incidence increase with COVID-19 ARDS compared to non-COVID, and is there association with shunt incidence and mortality? FindingsIn this prospective, observational cohort study, we showed no statistically significant difference in shunt prevalence between COVID-19 ARDS patients (17.0%) and non-COVID patients (22.7%). However, in COVID-19 patients, there was a difference in hospital mortality for those with shunt (54.8%) compared to those without shunt (35.8%), but this difference did not persist at 90-day mortality, nor after regression adjustments for age and illness severity. MeaningThere was no evidence of increased R-L shunt rates in COVID-19 compared to non-COVID or historical controls. Right-to-left shunt presence was associated with increased hospital mortality for COVID-19 patients, but this did not persist for 90-day mortality or after adjustment using logistic regression.
ABSTRACT
BackgroundSociodemographic and clinical factors are emerging as important predictors for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ObjectiveTo determine whether public health interventions that culminated in a stay-at-home lockdown instituted during the first wave of the pandemic in March/April 2020 were effective at mitigating the association of any of these factors with the risk of infection. DesignPopulation-based cohort study SettingOntario, Canada PatientsAll adults that underwent testing for SARS-CoV-2 between January 1 and June 12, 2020. MeasurementsThe outcome of interest was SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the peak of the pandemic to assess for changes in effect sizes. ResultsAmong 578,263 community-dwelling individuals, 20,524 (3.5%) people tested positive. The association between age and SARS-CoV-2 infection risk among tested community-dwelling individuals varied over time (P-interaction <0.0001). Prior to the first-wave peak of the pandemic, the likelihood of SARS-CoV-2 infection increased progressively with age compared with individuals aged 18-45 years (P<0.0001). This association subsequently reversed, with all age groups younger than 85 years at progressively higher risk of infection (P<0.0001) after the peak. Otherwise, risk factors that persisted throughout included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, and history of hypertension and diabetes. While there was a reduction in infection rates across Ontario after mid-April, there was less impact in regions with higher degrees of racial/ethnic diversity. When considered in an additive risk model, following the initial peak of the pandemic, individuals living in the most racially/ethnically diverse communities with 2, 3, or [≥]4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P<0.0001). In contrast, in the least racially/ethnically diverse communities, there was little to no gradient in infection rates across risk strata. ConclusionAfter public health interventions in March/April 2020, people with multiple risk factors residing in the most racially diverse communities of Ontario continued to have the highest likelihood of SARS-CoV-2 infection while risk was mitigated for people with multiple risk factors residing in less racially/ethnically diverse communities. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in these communities. Primary Funding SourceCanadian Institutes of Health Research and the Ted Rogers Centre for Heart Research.
