Geographically skewed recruitment and COVID-19 seroprevalence estimates: a cross-sectional serosurveillance study and mathematical modelling analysis.

OBJECTIVES: Convenience sampling is an imperfect but important tool for seroprevalence studies. For COVID-19, local geographic variation in cases or vaccination can confound studies that rely on the geographically skewed recruitment inherent to convenience sampling. The objectives of this study were: (1) quantifying how geographically skewed recruitment influences SARS-CoV-2 seroprevalence estimates obtained via convenience sampling and (2) developing new methods that employ Global Positioning System (GPS)-derived foot traffic data to measure and minimise bias and uncertainty due to geographically skewed recruitment. DESIGN: We used data from a local convenience-sampled seroprevalence study to map the geographic distribution of study participants' reported home locations and compared this to the geographic distribution of reported COVID-19 cases across the study catchment area. Using a numerical simulation, we quantified bias and uncertainty in SARS-CoV-2 seroprevalence estimates obtained using different geographically skewed recruitment scenarios. We employed GPS-derived foot traffic data to estimate the geographic distribution of participants for different recruitment locations and used this data to identify recruitment locations that minimise bias and uncertainty in resulting seroprevalence estimates. RESULTS: The geographic distribution of participants in convenience-sampled seroprevalence surveys can be strongly skewed towards individuals living near the study recruitment location. Uncertainty in seroprevalence estimates increased when neighbourhoods with higher disease burden or larger populations were undersampled. Failure to account for undersampling or oversampling across neighbourhoods also resulted in biased seroprevalence estimates. GPS-derived foot traffic data correlated with the geographic distribution of serosurveillance study participants. CONCLUSIONS: Local geographic variation in seropositivity is an important concern in SARS-CoV-2 serosurveillance studies that rely on geographically skewed recruitment strategies. Using GPS-derived foot traffic data to select recruitment sites and recording participants' home locations can improve study design and interpretation.

Mobile Health Services for COVID-19: Counseling, Testing, and Vaccination for Medically Underserved Populations.

Mobile health units can improve access to preventive health services, especially for medically underserved populations. However, there is little published experience of mobile health units being used to expand access to COVID-19 vaccination. In concert with local public health departments and community members, we implemented a mobile COVID-19 health unit and deployed it to 12 predominantly low-income and racial/ethnic minority communities in Massachusetts. We describe the success and challenges of this innovative program in expanding access to COVID-19 vaccination. (Am J Public Health. 2022;112(11):1556-1559. https://doi.org/10.2105/AJPH.2022.307021).

Expanding COVID-19 vaccine access to underserved populations through implementation of mobile vaccination units.

COVID-19 has disproportionately impacted underserved populations, including racial/ethnic minorities. Prior studies have demonstrated that mobile health units are effective at expanding preventive services for hard-to-reach populations, but this has not been studied in the context of COVID-19 vaccination. Our objective was to determine if voluntary participants who access mobile COVID-19 vaccination units are more likely to be racial/ethnic minorities and adolescents compared with the general vaccinated population. We conducted a cross-sectional study of individuals who presented to three different mobile COVID-19 vaccination units in the Greater Boston area from May 20, 2021, to August 18, 2021. We acquired data regarding the general vaccinated population in the state and of target communities from the Massachusetts Department of Public Health. We used chi-square testing to compare the demographic characteristics of mobile vaccination unit participants and the general state and community populations that received COVID-19 vaccines during the same time period. We found that during this three-month period, mobile vaccination units held 130 sessions and administered 2622 COVID-19 vaccine doses to 1982 unique participants. The median (IQR) age of participants was 31 (16-46) years, 1016 (51%) were female, 1575 (80%) were non-White, and 1126 (57%) were Hispanic. Participants in the mobile vaccination units were more likely to be younger (p < 0.001), non-White race (p < 0.001), and Hispanic ethnicity (p < 0.001) compared with the general vaccinated population of the state and target communities. This study suggests that mobile vaccination units have the potential to improve access to COVID-19 vaccination for diverse populations.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa

Background Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. Methods We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres;Contact Tracing (CT) in households of cases;Isolation Centres (IC), for cases not requiring hospitalisation;community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS);and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (R e ) of 1.5 and 1.2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER) <US$1,290/year-of-life saved (YLS) to be cost-effective. Findings With R e 1.5, HT resulted in the most COVID-19 deaths and lowest costs over 360 days. Compared with HT, HT+CT+IC+MS reduced mortality by 76%, increased costs by 16%, and was cost-effective (ICER $350/YLS). HT+CT+IC+MS+QC provided the greatest reduction in mortality, but increased costs by 95% compared with HT+CT+IC+MS and was not cost-effective (ICER $8,000/YLS). With R e 1.2, HT+CT+IC+MS was the least costly strategy, and HT+CT+IC+MS+QC was not cost-effective (ICER $294,320/YLS). Interpretation In South Africa, a strategy of household contact tracing, isolation, and mass symptom screening would substantially reduce COVID-19 mortality and be cost-effective. Adding quarantine centres for COVID-19 contacts is not cost-effective.

Clinical Impact, Costs, and Cost-effectiveness of Expanded Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Massachusetts.

BACKGROUND: We projected the clinical and economic impact of alternative testing strategies on coronavirus disease 2019 (COVID-19) incidence and mortality in Massachusetts using a microsimulation model. METHODS: We compared 4 testing strategies: (1) hospitalized: polymerase chain reaction (PCR) testing only for patients with severe/critical symptoms warranting hospitalization; (2) symptomatic: PCR for any COVID-19-consistent symptoms, with self-isolation if positive; (3) symptomatic + asymptomatic once: symptomatic and 1-time PCR for the entire population; and (4) symptomatic + asymptomatic monthly: symptomatic with monthly retesting for the entire population. We examined effective reproduction numbers (Re = 0.9-2.0) at which policy conclusions would change. We assumed homogeneous mixing among the Massachusetts population (excluding those residing in long-term care facilities). 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: At Re = 0.9, symptomatic + asymptomatic monthly vs hospitalized resulted in a 64% reduction in infections and a 46% reduction in deaths, but required >66-fold more tests/day with 5-fold higher costs. Symptomatic + asymptomatic monthly had an ICER <$100 000/QALY only when Re ≥1.6; when test cost was ≤$3, every 14-day testing was cost-effective at all Re examined. CONCLUSIONS: Testing people with any COVID-19-consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.

Association Between Prison Crowding and COVID-19 Incidence Rates in Massachusetts Prisons, April 2020-January 2021.

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 Participants: This 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 Measures: The 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 Relevance: This 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.

Preventing Infectious Complications of Immunomodulation in COVID-19 in Foreign-Born Patients.

Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.

College Campuses and COVID-19 Mitigation: Clinical and Economic Value.

BACKGROUND: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses. DESIGN: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions. DATA SOURCES: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours. TARGET POPULATION: Undergraduate students and faculty at U.S. colleges. TIME HORIZON: One semester (105 days). PERSPECTIVE: Modified societal. INTERVENTION: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening. OUTCOME MEASURES: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY). RESULTS OF BASE-CASE ANALYSIS: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600). RESULTS OF SENSITIVITY ANALYSIS: Results were most sensitive to test costs. LIMITATION: Data are from multiple sources. CONCLUSION: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic.

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19). Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness. Design, Setting, and Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020. Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention. Main Outcomes and Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented. Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs $3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs $0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs $0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6, $27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81% fewer infections (376) and 542% higher costs ($39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59% fewer infections (71) and 7114% higher costs ($38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. Conclusions and Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study.

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 (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re 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 (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. FINDINGS: When Re 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 Re 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 Re 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 tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations. FUNDING: US National Institutes of Health, Royal Society, Wellcome Trust.

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for People Experiencing Sheltered Homelessness During the COVID-19 Pandemic.

IMPORTANCE: Approximately 356,000 people stay in homeless shelters nightly in the US. They are at high risk for COVID-19. OBJECTIVE: To assess clinical outcomes, costs, and cost-effectiveness of strategies for COVID-19 management among sheltered homeless adults. DESIGN: We developed a dynamic microsimulation model of COVID-19 in sheltered homeless adults in Boston, Massachusetts. We used cohort characteristics and costs from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were from published literature and national databases. We examined surging, growing, and slowing epidemics (effective reproduction numbers [Re] 2.6, 1.3, and 0.9). Costs were from a health care sector perspective; time horizon was 4 months, from April to August 2020. SETTING & PARTICIPANTS: Simulated cohort of 2,258 adults residing in homeless shelters in Boston. INTERVENTIONS: We assessed daily symptom screening with polymerase chain reaction (PCR) testing of screen-positives, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternate care sites [ACSs] for mild/moderate COVID-19, and temporary housing, each compared to no intervention. MAIN OUTCOMES AND MEASURES: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case prevented of COVID-19. RESULTS: We simulated a population of 2,258 sheltered homeless adults with mean age of 42.6 years. Compared to no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild/moderate disease led to 37% fewer infections and 46% lower costs (Re=2.6), 75% fewer infections and 72% lower costs (Re=1.3), and 51% fewer infections and 51% lower costs (Re=0.9). Adding PCR testing every 2 weeks further decreased infections; incremental cost per case prevented was $1,000 (Re=2.6), $27,000 (Re=1.3), and $71,000 (Re=0.9). Temporary housing with PCR every 2 weeks was most effective but substantially more costly than other options. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. CONCLUSIONS & RELEVANCE: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer COVID-19 infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in COVID-19 infections at modest incremental cost and should be considered during future surges.

Thrombosis in COVID-19.

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.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study.

BACKGROUND: Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. METHODS: We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and molecular testing for symptomatic individuals (MS); and Quarantine Centres (QC), for household contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (Re) of 1·5 and 1·2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER)

Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System? A Call for Epidemiologic Investigations.

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.