Heparin for Moderately Ill Patients with Covid-19

BackgroundHeparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. MethodsWe randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. ResultsAt 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). ConclusionsIn moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days. Trial registration numbers: NCT04362085; NCT04444700

A disproportionate epidemic: COVID-19 cases and deaths among essential workers in Toronto, Canada

Shelter-in-place mandates and closure of non-essential businesses have been central to COVID-19 response strategies including in Toronto, Canada. Approximately half of the working population in Canada are employed in occupations that do not allow for remote work suggesting potentially limited impact of some of the strategies proposed to mitigate COVID-19 acquisition and onward transmission risks and associated morbidity and mortality. We compared per-capita rates of COVID-19 cases and deaths from January 23, 2020 to January 24, 2021, across neighborhoods in Toronto by proportion of the population working in essential services. We used person-level data on laboratory-confirmed COVID-19 community cases (N=74,477) and deaths (N=2319), and census data for neighborhood-level attributes. Cumulative per-capita rates of COVID-19 cases and deaths were 3-fold and 2.5-fold higher, respectively, in neighborhoods with the highest versus lowest concentration of essential workers. Findings suggest that the population who continued to serve the essential needs of society throughout COVID-19 shouldered a disproportionate burden of transmission and deaths. Taken together, results signal the need for active intervention strategies to complement restrictive measures to optimize both the equity and effectiveness of COVID-19 responses.

The mobility gap: estimating mobility levels required to control Canada's winter COVID-19 surge

BackgroundNon-pharmaceutical interventions remain a primary means of suppressing COVID-19 until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures in seven Canadian provinces to quantify the mobility level needed to suppress COVID-19 (mobility threshold), and the difference relative to current mobility levels (mobility gap). MethodsWe conducted a longitudinal study of weekly COVID-19 incidence from March 15, 2020 to January 16, 2021, among provinces with 20 COVID-19 cases in at least 10 weeks. The outcome was weekly growth rate defined as the ratio of current cases compared to the previous week. We examined the effects of average time spent outside the home (non-residential mobility) in the prior three weeks using a lognormal regression model accounting for province, season, and mean temperature. We calculated the COVID-19 mobility threshold and gap. ResultsAcross the 44-week study period, a total of 704,294 persons were infected with COVID-19. Non-residential mobility dropped rapidly in the spring and reached a median of 36% (IQR: 31,40) in April 2020. After adjustment, each 5% increase in non-residential mobility was associated with a 9% increase in the COVID-19 weekly growth rate (ratio=1.09, 95%CI: 1.07,1.12). The mobility gap increased through the fall months, which was associated with increasing case growth. InterpretationMobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control COVID-19 through winter 2021. Mobility measures from anonymized smartphone data can be used to guide the provincial and regional implementation and loosening of physical distancing measures.

Coronavirus-19 and coagulopathy: A Systematic Review

BackgroundUnderstanding the association between Coronavirus Disease 2019 (COVID-19) and coagulopathy may assist clinical prognostication, and influence treatment and outcomes. We aimed to systematically describe the relationship between hemostatic laboratory parameters and important clinical outcomes among adults with COVID-19. MethodsA systematic review of randomized clinical trials, observational studies and case series published in PubMed (Medline), EMBASE, and CENTRAL from December 1, 2019 to March 25, 2020. Studies of adult patients with COVID-19 that reported at least one hemostatic laboratory parameter were included. ResultsData were extracted from 57 studies (N=12,050 patients) that met inclusion criteria. The average age of patients was 52 years and 45% were women. Of the included studies, 92.7% (N=38/41 studies) reported an average platelet count [≥] 150 x 109/L, 68.2% (N=15/22 studies) reported an average prothrombin time (PT) between 11-14 s, 55% (N=11/20 studies) reported an average activated partial thromboplastin time (aPTT) between 25-35 s, and 34.4% (N=11/32 studies) reported a D-dimer concentration above the upper limit of normal (ULN). Eight studies (7 cohorts and 1 case series) reported hemostatic lab values for survivors versus non-survivors. Among non-survivors, D-dimer concentrations were reported in 4 studies and all reported an average above the ULN. InterpretationMost patients had a normal platelet count, elevated D-dimer, PT and aPTT values in the upper reference interval; D-dimer elevation appeared to correlate with poor outcomes. Further studies are needed to better correlate these hemostatic parameters with the risk of adverse outcomes such as thrombosis and bleeding.

Catching a resurgence: Increase in SARS-CoV-2 viral RNA identified in wastewater 48 hours before COVID-19 clinical tests and 96 hours before hospitalizations

Curtailing the Spring 2020 COVID-19 surge required sweeping and stringent interventions by governments across the world. Wastewater-based COVID-19 epidemiology programs have been initiated in many countries to provide public health agencies with a complementary disease tracking metric and facile surveillance tool. However, their efficacy in prospectively capturing resurgence following a period of low prevalence is unclear. In this study, the SARS-CoV-2 viral signal was measured in primary clarified sludge harvested every two days at the City of Ottawas water resource recovery facility during the summer of 2020, when clinical testing recorded daily percent positivity below 1%. In late July, increases of >400% in normalized SARS-CoV-2 RNA signal in wastewater were identified 48 hours prior to reported >300% increases in positive cases that were retrospectively attributed to community-acquired infections. During this resurgence period, SARS-CoV-2 RNA signal in wastewater preceded the reported >160% increase in community hospitalizations by approximately 96 hours. This study supports wastewater-based COVID-19 surveillance of populations in augmenting the efficacy of diagnostic testing, which can suffer from sampling biases or timely reporting as in the case of hospitalization census.