Long COVID and Medicine's Two Cultures.

Medicine has separated the two cultures of biological science and social science in research, even though they are intimately connected in the lives of our patients. To understand the cause, progression, and treatment of long COVID , biology and biography, the patient's lived experience, must be studied together.

Quarantine and serial testing for variants of SARS-CoV-2 with benefits of vaccination and boosting on consequent control of COVID-19.

Quarantine and serial testing strategies for a disease depend principally on its incubation period and infectiousness profile. In the context of COVID-19, these primary public health tools must be modulated with successive SARS CoV-2 variants of concern that dominate transmission. Our analysis shows that (1) vaccination status of an individual makes little difference to the determination of the appropriate quarantine duration of an infected case, whereas vaccination coverage of the population can have a substantial effect on this duration, (2) successive variants can challenge disease control efforts by their earlier and increased transmission in the disease time course relative to prior variants, and (3) sufficient vaccine boosting of a population substantially aids the suppression of local transmission through frequent serial testing. For instance, with Omicron, increasing immunity through vaccination and boosters-for instance with 100% of the population is fully immunized and at least 24% having received a third dose-can reduce quarantine durations by up to 2 d, as well as substantially aid in the repression of outbreaks through serial testing. Our analysis highlights the paramount importance of maintaining high population immunity, preferably by booster uptake, and the role of quarantine and testing to control the spread of SARS CoV-2.

Comparative analyses of eighteen rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation.

Background: Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies. Methods: We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data. Results: We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting. Conclusions: These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

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.

Allostatic load in the context of disasters.

Environmental disasters, pandemics, and other major traumatic events such as the Covid-19 pandemic or war contribute to psychosocial stress which manifests in a wide range of mental and physical consequences. The increasing frequency and severity of such events suggest that the adverse effects of toxic stress are likely to become more widespread and pervasive in the future. The allostatic load (AL) model has important elements that lend themselves well for identifying adverse health effects of disasters. Here we examine several articulations of AL from the standpoint of using AL to gauge short- and long-term health effects of disasters and to provide predictive capacity that would enable mitigation or prevention of some disaster-related health consequences. We developed a transdisciplinary framework combining indices of psychosocial AL and physiological AL to produce a robust estimate of overall AL in people affected by disasters and other traumatic events. In conclusion, we urge researchers to consider the potential of using AL as a component in a proposed disaster-oriented human health observing system.

Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study.

BACKGROUND: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy. METHODS: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0-14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as "sufficient." FINDINGS: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases. INTERPRETATION: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts. FUNDING: EasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families' endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM).

The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. METHODS: We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%-5.0%) from 9.0% (95% CrI: 8.4%-9.4%) without vaccination, over 300 days. The highest relative reduction (54%-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%-66.7%), 65.6% (95% CrI: 62.2%-68.6%), and 69.3% (95% CrI: 65.5%-73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.

The U.S. Needs a National Human Health Observing System.

The COVID-19 pandemic and increasing frequency and severity of environmental disasters reveal an urgent need for a robust health observing/surveillance system. With the possible exception of Brazil, we know of no such comprehensive health observing capacity. The US should create a national system of linked regionally-based health monitoring systems similar to those for weather, ocean conditions, and climate. Like those for weather, the health observing system should operate continuously, collecting mental, physical, and community health data before, during, and after events. The system should include existing cross-sectional health data surveys, along with significant new investment in regional longitudinal cohort studies. The recently described framework for a Gulf of Mexico Community Health Observing System is suggested as a potential model for development of a nation-wide system.

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.

The human gut microbiome and health inequities.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.

Accelerated vaccine rollout is imperative to mitigate highly transmissible COVID-19 variants.

BACKGROUND: More contagious variants of SARS-CoV-2 have emerged around the world, sparking concerns about impending surge in cases and severe outcomes. Despite the development of effective vaccines, rollout has been slow. We evaluated the impact of accelerated vaccine distribution on curbing the disease burden of novel SARS-CoV-2 variants. METHODS: We used an agent-based model of SARS-CoV-2 transmission and vaccination to simulate the spread of novel variants with S-Gene Target Failure (SGTF) in addition to the original strain. We incorporated age-specific risk and contact patterns and implemented a two-dose vaccination campaign in accord with CDC-recommended prioritization. As a base case, we projected hospitalizations and deaths at a daily vaccination rate of 1 million doses in the United States (US) and compared with accelerated campaigns in which daily doses were expanded to 1.5, 2, 2.5, or 3 million. FINDINGS: We found that at a vaccination rate of 1 million doses per day, an emergent SGTF variant that is 20-70% more transmissible than the original variant would become dominant within 2 to 9 weeks, accounting for as much as 99% of cases at the outbreak peak. Our results show that accelerating vaccine delivery would substantially reduce severe health outcomes. For a SGTF with 30% higher transmissibility, increasing vaccine doses from 1 to 3 million per day would avert 152,048 (95% CrI: 134,772-168,696) hospitalizations and 48,448 (95% CrI: 42,042-54,285) deaths over 300 days. Accelerated vaccination would also prevent additional COVID-19 waves that would otherwise be fuelled by waning adherence to non-pharmaceutical interventions (NPIs). INTERPRETATION: We found that the current pace of vaccine rollout is insufficient to prevent the exacerbation of the pandemic that will be attributable to the novel, more contagious SARS-CoV-2 variants. Accelerating the vaccination rate should be a public health priority for averting the expected surge in COVID-19 hospitalizations and deaths that would be associated with widespread dissemination of the SGTF variants. Our results underscore the need to bolster the production and distribution of COVID-19 vaccines, to rapidly expand vaccination priority groups and distribution sites.

Spatiotemporal pattern of COVID-19 spread in Brazil.

Brazil has been severely hit by COVID-19, with rapid spatial spread of both cases and deaths. We used daily data on reported cases and deaths to understand, measure, and compare the spatiotemporal pattern of the spread across municipalities. Indicators of clustering, trajectories, speed, and intensity of the movement of COVID-19 to interior areas, combined with indices of policy measures, show that although no single narrative explains the diversity in the spread, an overall failure of implementing prompt, coordinated, and equitable responses in a context of stark local inequalities fueled disease spread. This resulted in high and unequal infection and mortality burdens. With a current surge in cases and deaths and several variants of concern in circulation, failure to mitigate the spread could further aggravate the burden.

Optimal COVID-19 quarantine and testing strategies.

For COVID-19, it is vital to understand if quarantines shorter than 14 days can be equally effective with judiciously deployed testing. Here, we develop a mathematical model that quantifies the probability of post-quarantine transmission incorporating testing into travel quarantine, quarantine of traced contacts with an unknown time of infection, and quarantine of cases with a known time of exposure. We find that testing on exit (or entry and exit) can reduce the duration of a 14-day quarantine by 50%, while testing on entry shortens quarantine by at most one day. In a real-world test of our theory applied to offshore oil rig employees, 47 positives were obtained with testing on entry and exit to quarantine, of which 16 had tested negative at entry; preventing an expected nine offshore transmission events that each could have led to outbreaks. We show that appropriately timed testing can make shorter quarantines effective.

Projection de la demande de lits de soins intensifs durant l'épidémie de COVID-19 au Canada.

CONTEXTE: La hausse des cas de maladie à coronavirus 2019 (COVID-19) au Canada peut créer une forte demande de soins hospitaliers et de soins intensifs. Nous avons évalué la mesure dans laquelle l'isolement volontaire des personnes présentant des symptômes légers retarde le sommet épidémique et réduit la demande de soins dans chaque province canadienne. MÉTHODES: Nous avons conçu un modèle de calcul et fait des simulations de la propagation de la COVID-19 dans chaque province. À partir des estimations des caractéristiques de la COVID-19, nous avons évalué la demande de lits d'hôpital et de lits de soins intensifs en l'absence d'isolement volontaire en supposant une moyenne de 2,5 cas secondaires, et avons comparé des scénarios en faisant varier le taux d'isolement volontaire des cas légers 24 heures après l'apparition des symptômes. RÉSULTATS: En l'absence d'isolement volontaire, l'épidémie atteindrait son sommet dans la première moitié de juin, et il faudrait en moyenne 569 jours-lits de soins intensifs par 10 000 habitants. Avec un taux d'isolement volontaire de 20 %, l'atteinte du sommet serait repoussée de 2 à 4 semaines, et la demande de lits diminuerait de 23,5 %; avec un taux de 40 %, le sommet serait repoussé de 2 à 4 semaines supplémentaires, et la demande de lits connaîtrait une baisse de 53,6 %. En fixant le taux d'occupation actuel des lits de soins intensifs à plus de 80 % et le taux d'isolement volontaire à 40 %, la demande de lits demeure supérieure au nombre de lits disponibles. INTERPRÉTATION: Au sommet de l'épidémie de COVID-19 au Canada, la demande de lits de soins intensifs excédera le nombre total de lits disponibles, même avec un taux d'isolement volontaire de 40 %. Nos résultats montrent que la situation sera difficile pour le système de santé et que l'isolement volontaire pourrait réduire la demande de soins hospitaliers et de soins intensifs.

The impact of vaccination on COVID-19 outbreaks in the United States.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States (US). METHODS: We developed an agent-based model of SARS-CoV-2 transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, while children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection, and specified 10% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current non-pharmaceutical interventions in the US. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% CrI: 4.3% - 5.0%) from 9.0% (95% CrI: 8.4% - 9.4%) without vaccination, over 300 days. The highest relative reduction (54-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-ICU hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3% - 66.7%), 65.6% (95% CrI: 62.2% - 68.6%), and 69.3% (95% CrI: 65.5% - 73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with non-pharmaceutical interventions is essential to achieve this impact.

The interplay of movement and spatiotemporal variation in transmission degrades pandemic control.

Successful public health regimes for COVID-19 push below unity long-term regional Rt -the average number of secondary cases caused by an infectious individual. We use a susceptible-infectious-recovered (SIR) model for two coupled populations to make the conceptual point that asynchronous, variable local control, together with movement between populations, elevates long-term regional Rt , and cumulative cases, and may even prevent disease eradication that is otherwise possible. For effective pandemic mitigation strategies, it is critical that models encompass both spatiotemporal heterogeneity in transmission and movement.

Framework for a Community Health Observing System for the Gulf of Mexico Region: Preparing for Future Disasters.

The Gulf of Mexico (GoM) region is prone to disasters, including recurrent oil spills, hurricanes, floods, industrial accidents, harmful algal blooms, and the current COVID-19 pandemic. The GoM and other regions of the U.S. lack sufficient baseline health information to identify, attribute, mitigate, and facilitate prevention of major health effects of disasters. Developing capacity to assess adverse human health consequences of future disasters requires establishment of a comprehensive, sustained community health observing system, similar to the extensive and well-established environmental observing systems. We propose a system that combines six levels of health data domains, beginning with three existing, national surveys and studies plus three new nested, longitudinal cohort studies. The latter are the unique and most important parts of the system and are focused on the coastal regions of the five GoM States. A statistically representative sample of participants is proposed for the new cohort studies, stratified to ensure proportional inclusion of urban and rural populations and with additional recruitment as necessary to enroll participants from particularly vulnerable or under-represented groups. Secondary data sources such as syndromic surveillance systems, electronic health records, national community surveys, environmental exposure databases, social media, and remote sensing will inform and augment the collection of primary data. Primary data sources will include participant-provided information via questionnaires, clinical measures of mental and physical health, acquisition of biological specimens, and wearable health monitoring devices. A suite of biomarkers may be derived from biological specimens for use in health assessments, including calculation of allostatic load, a measure of cumulative stress. The framework also addresses data management and sharing, participant retention, and system governance. The observing system is designed to continue indefinitely to ensure that essential pre-, during-, and post-disaster health data are collected and maintained. It could also provide a model/vehicle for effective health observation related to infectious disease pandemics such as COVID-19. To our knowledge, there is no comprehensive, disaster-focused health observing system such as the one proposed here currently in existence or planned elsewhere. Significant strengths of the GoM Community Health Observing System (CHOS) are its longitudinal cohorts and ability to adapt rapidly as needs arise and new technologies develop.

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.