Mortality and morbidity ramifications of proposed retractions in healthcare coverage for the United States.

In the absence of universal healthcare in the United States, federal programs of Medicaid and Medicare are vital to providing healthcare coverage for low-income households and elderly individuals, respectively. However, both programs are under threat, with either enacted or proposed retractions. Specifically, raising Medicare age eligibility and the addition of work requirements for Medicaid qualification have been proposed, while termination of continuous enrollment for Medicaid was recently effectuated. Here, we assess the potential impact on mortality and morbidity resulting from these policy changes. Our findings indicate that the policy change to Medicare would lead to over 17,000 additional deaths among individuals aged 65 to 67 and those to Medicaid would lead to more than 8,000 deaths among those under the age of 65. To illustrate the implications for morbidity, we further consider a case study among those people with diabetes who would be likely to lose their health insurance under the policy changes. We project that these insurance retractions would lead to the loss of coverage for over 700,000 individuals with diabetes, including more than 200,000 who rely on insulin.

Estimating the lives that could be saved by expanded access to weight-loss drugs.

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments.

Disease burden among Ukrainians forcibly displaced by the 2022 Russian invasion.

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraine's 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

Large numbers cause magnitude neglect: The case of government expenditures.

Four studies demonstrate that the public's understanding of government budgetary expenditures is hampered by difficulty in representing large numerical magnitudes. Despite orders of magnitude difference between millions and billions, study participants struggle with the budgetary magnitudes of government programs. When numerical values are rescaled as smaller magnitudes (in the thousands or lower), lay understanding improves, as indicated by greater sensitivity to numerical ratios and more accurate rank ordering of expenses. A robust benefit of numerical rescaling is demonstrated across a variety of experimental designs, including policy relevant choices and incentive-compatible accuracy measures. This improved sensitivity ultimately impacts funding choices and public perception of respective budgets, indicating the importance of numerical cognition for good citizenship.

The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2.

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

Evaluation of Strategies for Transitioning to Annual SARS-CoV-2 Vaccination Campaigns in the United States.

BACKGROUND: The U.S. Food and Drug Administration has proposed administering annual SARS-CoV-2 vaccines. OBJECTIVE: To evaluate the effectiveness of an annual SARS-CoV-2 vaccination campaign, quantify the health and economic benefits of a second dose provided to children younger than 2 years and adults aged 50 years or older, and optimize the timing of a second dose. DESIGN: An age-structured dynamic transmission model. SETTING: United States. PARTICIPANTS: A synthetic population reflecting demographics and contact patterns in the United States. INTERVENTION: Vaccination against SARS-CoV-2 with age-specific uptake similar to that of influenza vaccination. MEASUREMENTS: Incidence, hospitalizations, deaths, and direct health care cost. RESULTS: The optimal timing between the first and second dose delivered to children younger than 2 years and adults aged 50 years or older in an annual vaccination campaign was estimated to be 5 months. In direct comparison with a single-dose campaign, a second booster dose results in 123 869 fewer hospitalizations (95% uncertainty interval [UI], 121 994 to 125 742 fewer hospitalizations) and 5524 fewer deaths (95% UI, 5434 to 5613 fewer deaths), averting $3.63 billion (95% UI, $3.57 billion to $3.69 billion) in costs over a single year. LIMITATIONS: Population immunity is subject to degrees of immune evasion for emerging SARS-CoV-2 variants. The model was implemented in the absence of nonpharmaceutical interventions and preexisting vaccine-acquired immunity. CONCLUSION: The direct health care costs of SARS-CoV-2, particularly among adults aged 50 years or older, would be substantially reduced by administering a second dose 5 months after the initial dose. PRIMARY FUNDING SOURCE: Natural Sciences and Engineering Research Council of Canada, Notsew Orm Sands Foundation, National Institutes of Health, Centers for Disease Control and Prevention, and National Science Foundation.

Universal healthcare as pandemic preparedness: The lives and costs that could have been saved during the COVID-19 pandemic.

The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. During a pandemic, the lives saved and economic benefits of a single-payer universal healthcare system relative to the status quo would be even greater. For Americans who are uninsured and underinsured, financial barriers to COVID-19 care delayed diagnosis and exacerbated transmission. Concurrently, deaths beyond COVID-19 accrued from the background rate of uninsurance. Universal healthcare would alleviate the mortality caused by the confluence of these factors. To evaluate the repercussions of incomplete insurance coverage in 2020, we calculated the elevated mortality attributable to the loss of employer-sponsored insurance and to background rates of uninsurance, summing with the increased COVID-19 mortality due to low insurance coverage. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved about 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a single-payer universal healthcare system over the course of the pandemic. These economic benefits are in addition to US$438 billion expected to be saved by single-payer universal healthcare during a nonpandemic year.

Public Health Impact of Paxlovid as Treatment for COVID-19, United States.

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.

Evaluation of COVID-19 vaccination strategies with a delayed second dose.

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis.

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.

Cost-effectiveness of Prefusion F Protein-based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States.

BACKGROUND: Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines. METHODS: We developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the United States. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained as a measure of effectiveness and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective. RESULTS: Using a willingness-to-pay of $95 000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD up to $127 with Arexvy and $118 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the United States, the budget impact of these programs at the maximum PPD ranged from $6.48 to $6.78 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $235 for Arexvy and $245 for Abrysvo, with 2-year budget impacts of $11.78 and $12.25 billion, respectively. CONCLUSIONS: Vaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.

The implications of silent transmission for the control of COVID-19 outbreaks.

Since the emergence of coronavirus disease 2019 (COVID-19), unprecedented movement restrictions and social distancing measures have been implemented worldwide. The socioeconomic repercussions have fueled calls to lift these measures. In the absence of population-wide restrictions, isolation of infected individuals is key to curtailing transmission. However, the effectiveness of symptom-based isolation in preventing a resurgence depends on the extent of presymptomatic and asymptomatic transmission. We evaluate the contribution of presymptomatic and asymptomatic transmission based on recent individual-level data regarding infectiousness prior to symptom onset and the asymptomatic proportion among all infections. We found that the majority of incidences may be attributable to silent transmission from a combination of the presymptomatic stage and asymptomatic infections. Consequently, even if all symptomatic cases are isolated, a vast outbreak may nonetheless unfold. We further quantified the effect of isolating silent infections in addition to symptomatic cases, finding that over one-third of silent infections must be isolated to suppress a future outbreak below 1% of the population. Our results indicate that symptom-based isolation must be supplemented by rapid contact tracing and testing that identifies asymptomatic and presymptomatic cases, in order to safely lift current restrictions and minimize the risk of resurgence.

Prosocial polio vaccination in Israel.

Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel's having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children-who had only received the inactivated polio vaccine-with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual's comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.

Projecting hospital utilization during the COVID-19 outbreaks in the United States.

In the wake of community coronavirus disease 2019 (COVID-19) transmission in the United States, there is a growing public health concern regarding the adequacy of resources to treat infected cases. Hospital beds, intensive care units (ICUs), and ventilators are vital for the treatment of patients with severe illness. To project the timing of the outbreak peak and the number of ICU beds required at peak, we simulated a COVID-19 outbreak parameterized with the US population demographics. In scenario analyses, we varied the delay from symptom onset to self-isolation, the proportion of symptomatic individuals practicing self-isolation, and the basic reproduction number R0 Without self-isolation, when R0 = 2.5, treatment of critically ill individuals at the outbreak peak would require 3.8 times more ICU beds than exist in the United States. Self-isolation by 20% of cases 24 h after symptom onset would delay and flatten the outbreak trajectory, reducing the number of ICU beds needed at the peak by 48.4% (interquartile range 46.4-50.3%), although still exceeding existing capacity. When R0 = 2, twice as many ICU beds would be required at the peak of outbreak in the absence of self-isolation. In this scenario, the proportional impact of self-isolation within 24 h on reducing the peak number of ICU beds is substantially higher at 73.5% (interquartile range 71.4-75.3%). Our estimates underscore the inadequacy of critical care capacity to handle the burgeoning outbreak. Policies that encourage self-isolation, such as paid sick leave, may delay the epidemic peak, giving a window of time that could facilitate emergency mobilization to expand hospital capacity.

Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak.

The novel coronavirus outbreak (COVID-19) in mainland China has rapidly spread across the globe. Within 2 mo since the outbreak was first reported on December 31, 2019, a total of 566 Severe Acute Respiratory Syndrome (SARS CoV-2) cases have been confirmed in 26 other countries. Travel restrictions and border control measures have been enforced in China and other countries to limit the spread of the outbreak. We estimate the impact of these control measures and investigate the role of the airport travel network on the global spread of the COVID-19 outbreak. Our results show that the daily risk of exporting at least a single SARS CoV-2 case from mainland China via international travel exceeded 95% on January 13, 2020. We found that 779 cases (95% CI: 632 to 967) would have been exported by February 15, 2020 without any border or travel restrictions and that the travel lockdowns enforced by the Chinese government averted 70.5% (95% CI: 68.8 to 72.0%) of these cases. In addition, during the first three and a half weeks of implementation, the travel restrictions decreased the daily rate of exportation by 81.3% (95% CI: 80.5 to 82.1%), on average. At this early stage of the epidemic, reduction in the rate of exportation could delay the importation of cases into cities unaffected by the COVID-19 outbreak, buying time to coordinate an appropriate public health response.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

Economic evaluation of COVID-19 rapid antigen screening programs in the workplace.

BACKGROUND: Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective. METHODS: To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults. RESULTS: Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening. CONCLUSIONS: Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.

Resolving the apparent transmission paradox of African sleeping sickness.

Human African trypanosomiasis (HAT), or African sleeping sickness, is a fatal disease found throughout sub-Saharan Africa. The disease is close to elimination in many areas, although it was similarly close to elimination once before and subsequently reemerged, despite seemingly low rates of transmission. Determining how these foci persisted and overcame an apparent transmission paradox is key to finally eliminating HAT. By assessing clinical, laboratory, and mathematical data, we propose that asymptomatic infections contribute to transmission through the presence of an overlooked reservoir of skin-dwelling parasites. Our assessment suggests that a combination of asymptomatic and parasitaemic cases is sufficient to maintain transmission at foci without animal reservoirs, and we argue that the current policy not to treat asymptomatic HAT should be reconsidered.

Mechanistic basis of post-treatment control of SIV after anti-α4ß7 antibody therapy.

Treating macaques with an anti-α4ß7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4ß7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4ß7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4ß7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4ß7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed-some animals exhibited large fluctuations in viral load after cART cessation-the model suggests that anti-α4ß7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

Population Immunity Against COVID-19 in the United States.

BACKGROUND: As of 28 July 2021, 60% of adults in the United States had been fully vaccinated against COVID-19, and more than 34 million cases had been reported. Given the uncertainty regarding undocumented infections, the population level of immunity against COVID-19 in the United States remains undetermined. OBJECTIVE: To estimate the population immunity, defined as the proportion of the population that is protected against SARS-CoV-2 infection due to prior infection or vaccination. DESIGN: Statistical and simulation modeling to estimate overall and age-specific population immunity. SETTING: United States. PARTICIPANTS: Simulated age-stratified population representing U.S. demographic characteristics. MEASUREMENTS: The true number of SARS-CoV-2 infections in the United States was inferred from data on reported deaths using age-specific infection-fatality rates (IFRs). Taking into account the estimates for vaccine effectiveness and protection against reinfection, the overall population immunity was determined as the sum of protection levels in vaccinated persons and those who were previously infected but not vaccinated. RESULTS: Using age-specific IFR estimates from the Centers for Disease Control and Prevention, it was estimated that as of 15 July 2021, 114.9 (95% credible interval [CrI], 103.2 to 127.4) million persons had been infected with SARS-CoV-2 in the United States. The mean overall population immunity was 62.0% (CrI, 58.4% to 66.4%). Adults aged 65 years or older were estimated to have the highest immunity level (77.2% [CrI, 76.2% to 78.6%]), and children younger than 12 years had the lowest immunity level (17.9% [CrI, 14.4% to 21.9%]). LIMITATION: Publicly reported deaths may underrepresent actual deaths. CONCLUSION: As of 15 July 2021, the U.S. population immunity against COVID-19 may still have been insufficient to contain the outbreaks and safely revert to prepandemic social behavior. PRIMARY FUNDING SOURCE: National Science Foundation, National Institutes of Health, Notsew Orm Sands Foundation, Canadian Institutes of Health Research, and Natural Sciences and Engineering Research Council of Canada.