Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

City-level GFT shows strong correlation with influenza cases and ED ILI visits, validating its use as an ED surveillance tool. GFT correlated with several pediatric ED crowding measures and those for low-acuity adult patients.

Thrombotic complications are frequent in COVID-19 and contribute significantly to mortality and morbidity. We review several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID-19. These include immune-mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin-angiotensin system dysregulation. We highlight biomarkers within each pathway with potential prognostic value in COVID-19. Lastly, recent observational studies have evaluated a role for the expanded use of therapeutic anticoagulation in COVID-19. We review strengths and weaknesses of these studies, and we also discuss the hypothetical benefit and anticipated challenges of fibrinolytic therapy in COVID-19. 2 | OVERVIEW OF COVID-19 ASSOCIATED HYPERCOAGULOPATHY Coronavirus disease 2019 induces a prothrombotic state, and a high frequency of reported major thrombotic events raises concern for unique

Background Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa. Methods We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number ( R e ) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an R e of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters ( R e values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. Findings When R e was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When R e was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which R e was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced. Interpretation In South Africa, strategies involving household contact trac...

Many colleges and universities in the United States are attempting to continue undergraduate onsite learning and residential living during the COVID-19 pandemic. Modeling the outcomes, cost, and cost-effectiveness of mitigation strategies, such as social distancing, masking, and laboratory testing, can inform these efforts.

IMPORTANCE COVID-19 incidence and mortality are higher among incarcerated persons than in the general US population, but the extent to which prison crowding contributes to their COVID-19 risk is unknown.OBJECTIVE To estimate the associations between prison crowding, community COVID-19 transmission, and prison incidence rates of COVID-19. DESIGN, SETTING, AND PARTICIPANTSThis was a longitudinal ecological study among all incarcerated persons in 14 Massachusetts state prisons between April 21, 2020, and January 11, 2021.EXPOSURES The primary exposure of interest was prison crowding, measured by (1) the size of the incarcerated population as a percentage of the prison's design capacity and (2) the percentage of incarcerated persons housed in single-cell units. The analysis included the weekly COVID-19 incidence in the county where each prison is located as a covariate. MAIN OUTCOMES AND MEASURESThe primary outcome was the weekly COVID-19 incidence rate as determined by positive SARS-CoV-2 tests among incarcerated persons at each prison over discrete 1-week increments.RESULTS There was on average 6876 people incarcerated in 14 prisons during the study period. The median level of crowding during the observation period ranged from 25% to 155% of design capacity. COVID-19 incidence was significantly higher in prisons where the incarcerated population was a larger percentage of the prison's design capacity (incidence rate ratio [IRR] per 10-percentage-point difference, 1.14; 95% CI, 1.03-1.27). COVID-19 incidence was lower in prisons where a higher proportion of incarcerated people were housed in single-cell units (IRR for each 10-percentage-point increase in single-cell units, 0.82; 95% CI, 0.73-0.93). COVID-19 transmission in the surrounding county was consistently associated with COVID-19 incidence in prisons (IRR [for each increase of 10 cases per 100 000 person-weeks in the community], 1.06; 95% CI, 1.05-1.08). CONCLUSIONS AND RELEVANCEThis longitudinal ecological study found that within 14 Massachusetts state prisons, increased crowding was associated with increased incidence rates of COVID-19. Researchers and policy makers should explore strategies that reduce prison crowding, such as decarceration, as potential ways to mitigate COVID-19 morbidity and mortality among incarcerated persons.

Background We projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model. Methods We compared five testing strategies: 1) PCR-severe-only: PCR testing only patients with severe/critical symptoms; 2) Self-screen: PCR-severe-only plus self-assessment of COVID-19-consistent symptoms with self-isolation if positive; 3) PCR-any-symptom: PCR for any COVID-19-consistent symptoms with self-isolation if positive; 4) PCR-all: PCR-any-symptom and one-time PCR for the entire population; and, 5) PCR-all-repeat: PCR-all with monthly re-testing. We examined effective reproduction numbers (Re, 0.9-2.0) at which policy conclusions would change. We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Results In all scenarios, PCR-all-repeat would lead to the best clinical outcomes and PCR-severe-only would lead to the worst; at Re 0.9, PCR-all-repeat vs. PCR-severe-only resulted in a 63% reduction in infections and a 44% reduction in deaths, but required >65-fold more tests/day with 4-fold higher costs. PCR-all-repeat had an ICER <$100,000/QALY only when Re≥1.8. At all Re values, PCR-any-symptom was cost-saving compared to other strategies. Conclusions Testing people with any COVID-19-consistent symptoms would be cost-saving compared to restricting testing to only those with symptoms severe enough to warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Universal screening would be cost-effective when paired with monthly retesting in settings where the COVID-19 pandemic is surging.

Key Points Question What are the projected clinical outcomes and costs associated with strategies for reducing severe acute respiratory syndrome coronavirus 2 infections among people experiencing sheltered homelessness? Findings In this decision analytic model, daily symptom screening with polymerase chain reaction (PCR) testing of individuals who had positive symptom screening paired with nonhospital care site management of people with mild to moderate coronavirus disease 2019 (COVID-19) was associated with a substantial decrease in infections and lowered costs over 4 months compared with no intervention across a wide range of epidemic scenarios. In a surging epidemic, adding periodic universal PCR testing to symptom screening and nonhospital care site management was associated with improved clinical outcomes at modestly increased costs. Meaning In this study, daily symptom screening with PCR testing of individuals who had positive symptom screening and use of alternative care sites for COVID-19 management among individuals experiencing sheltered homelessness were associated with substantially reduced new cases and costs compared with other strategies.