Equity in healthcare today

Equity in healthcare today

Equity in healthcare today. I note cases are growing fastest here in NW England but R values are an over-estimate according to Alastair Grant. Bangkok is amongst many places to have cancelled New Year’s celebrations and cases are climbing in Xi’An in China (206 yesterday) so they’re going into a lockdown locally as zero covid is the priority. 1,171 flights have been cancelled over Xmas in the US and about 1000 people in Sydney have been incorrectly told they have negative test results. Many are saying endemic covid should be a cause for celebration not consternation. Humans have a natural tendency to experience losses, even perceived ones, with far more intensity than they experience gains. In that context, it’s understandable that the “endemic” label smacks of failure rather than victory. Through a combination of increased vaccinations, booster shots and new antiviral treatments, the likelihood of dying from endemic COVID-19 will be 90% to 95% lower than in early 2020. That reflects a mortality rate somewhere between 0.05 percent and 0.1 percent, similar to what many experience with the flu. This is thanks largely to vaccines and our behaviour. Here’s the bear case versus vaccines, never mind minor details like boosters prevent hospitalisations and son of Omicron may be pretty close to Omicron:

https://www.nakedcapitalism.com/2021/12/maybe-no-omicron-boosters.html

In other news to start the week here’s a great review on the history, aims and vision of the James Webb space telescope:

https://www.quantamagazine.org/why-nasas-james-webb-space-telescope-matters-so-much-20211203

According to Alex Selby: “The tell-tale sign in the epidemiology for a shorter generation time would be the growth rates narrowing as people reduce contacts and stay at home more, and arguably that is what we're seeing now”:

A paper shows that accounting for under-detection of infection, infection seasonality, nonpharmaceutical interventions, and vaccination, they estimate that the majority of South Africans had been infected by SARS-CoV-2 before the Omicron wave. Based on findings for Gauteng province, Omicron is estimated 100.3% (95% CI: 16 74.8 - 140.4%) more transmissible than the ancestral SARS-CoV-2 and 36.5% (95% CI: 20.9 - 17 60.1%) more transmissible than Delta; in addition, Omicron erodes 63.7% (95% CI: 52.9 - 73.9%) of the population immunity, accumulated from prior infections and vaccination, in Gauteng:

http://www.columbia.edu/~jls106/yang_shaman_omicron_sa.pdf

Researchers asked to what extent did the COVID-19 pandemic reduce access to surgical care, and were racial and ethnic minority groups more likely to have reduced access to surgical care? In this cohort study of more than 13 million inpatient and outpatient surgical encounters in 767 US hospitals in a hospital administrative database, surgical use was 13% lower in 2020 compared with 2019, with the greatest decrease concentrated in elective surgical procedures. While Black and Hispanic patients experienced a reduction in surgical encounters, White patients experienced the greatest reduction in surgical encounters. Despite severe and persistent disruptions to health systems during the COVID-19 pandemic, racial and ethnic minority groups did not experience a disproportionate decrease in access to surgical care:

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2787470

How did hospitalisations and racial and ethnic disparities in hospitalisation outcomes change during the COVID-19 pandemic among patients with traditional Medicare? In this cohort study using 100% traditional Medicare inpatient data, comprising 31 771 054 beneficiaries and 14 021 285 hospitalisations from January 2019 through February 2021, the decline in non–COVID-19 and emergence of COVID-19 hospitalisations during the pandemic was qualitatively similar among beneficiaries of different racial and ethnic minority groups. In-hospital mortality for patients with COVID-19 was higher in racial and ethnic minority groups than in White patients, driven by a Hispanic-White gap; mortality among non-COVID-19 hospitalisations also differentially increased among patients in racial and ethnic minority groups relative to White patients, driven by an increased Black-White gap. Racial and ethnic disparities in mortality were evident among COVID-19 hospitalisations and widened among non–COVID-19 hospitalisations among Medicare beneficiaries, motivating greater attention to health equity:

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2787469

Is exposure to incarceration associated with a long-term increase in mortality rate, and does this association differ by race? In this cohort study of 7974 individuals who were followed up from 1979 to 2018, incarceration was associated with a 65% higher mortality rate among Black participants. Among non-Black participants, incarceration was not associated with mortality. These findings suggest that racial disparities in the association of incarceration with mortality, as well as in rates of exposure to incarceration, may partially explain the lower life expectancy of the non-Hispanic Black population in the US:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787436

Next, are youths with a history of incarceration at increased risk of early mortality compared with youths with no history of incarceration? In this cohort study of 3645 previously incarcerated youths, the all-cause mortality rate was 5.9 times higher in previously incarcerated youths than the rate observed in general population, Medicaid-enrolled youths. Homicide was the leading cause of death among formerly incarcerated youths, accounting for more deaths than all other causes combined. These findings suggest that delinquency and violence prevention strategies that incorporate a culturally informed approach and consider sex and developmental level are critical to reduce early mortality in this high-risk youth population:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787434

These studies shed light on the association between incarceration and mortality. The first group explore the association between incarceration and mortality using cohort data from the National Longitudinal Survey of Youth (NLSY79) from 1979 to 2018. They found that, nationally, exposure to incarceration was associated with a significant increase in mortality among Black participants compared with non-Black participants (adjusted hazard ratio, 1.65). The authors interpret their findings in the context of structural racism, wherein the disproportionate incarceration of African Americans is deeply connected to underlying socioeconomic risk factors. They suggest that incarceration is a key mechanism in life-expectancy differences between Black and other populations, and as such, the prison system, as well as the overexposure of African Americans to it, constitutes a crucial focal point for social and health policy intervention.

The second study followed up a cohort of incarcerated youth in Ohio from 2010 to 2017 to investigate how their mortality rates contrast with nonincarcerated peers who were enrolled in Medicaid. They found that the all-cause mortality rate for incarcerated youth was significantly higher than that for Medicaid-enrolled youth (adjusted incidence rate ratio, 5.91), with Black youth more likely to die from homicide, while White youth were more likely to die at higher rates from suicide and drug overdose. An important finding from their study is that previously incarcerated young women have significantly higher risks of early adult mortality; the all-cause mortality risk for these women was nearly 9 times that of their comparison group.

Furthermore, both studies incorporate a discussion of how societal conditions contribute to the mortality and morbidity of their participants. In a landmark demographic study, Evelyn Patterson analysed the death rates of prisoners by gender and race and found that Black male prisoners experienced lower mortality rates in prison than their nonincarcerated counterparts, even after accounting for deaths within the nonincarcerated population that are attributable to firearms and motor vehicle crashes. Patterson posits that for Black populations, access to nutrition and health care, even outside of prison, is so deficient that the minimal care Black prisoners receive while incarcerated may decrease risks of mortality, even as they are exposed to the intra-prison spread of diseases. Thus, Patterson’s work demonstrates the inextricable links between conditions of socioeconomic inequality found in civil society that affect health and mortality for Black populations and those found within the prison system. The studies above support Patterson’s findings by suggesting that a study of health disparities among incarcerated youth ought to include a closer analysis of social conditions outside of prison.

Decarceration must be a policy consideration, even as access to health care improves behind bars. However, making improvements to carceral institutions all too often expands an already far-reaching system of mass incarceration. Not all policy interventions necessitate an expansion of prison facilities. Reducing the number of incarcerated adults and youth, coupled with investing in community support and much needed economic opportunity, is a potential strategy for mitigating racial disparities in health and mortality among individuals contained in correctional facilities.

Lastly, the findings include data collected before the COVID-19 pandemic. Research shows that the cumulative mortality rate ratio of prisoner deaths was 2.5 times higher than the US population. However, it is unknown how the penal system structured racial disparities in COVID-19 deaths within prisons and between prisoners, given observed racial segregation in housing and cell units, leading to what Brittany Friedman calls “death by design” within penal institutions. In short, they provide a critical examination of racial inequality in youth and adult mortality among detained and incarcerated people. They highlight policy interventions to decrease mortality, including firearm education, violence prevention programs, a higher standard of medical care, and a wide range of sociological factors, such as social inequality, residential segregation, and economic inequality. Their recommendations are important for improving health and mortality outcomes among people exposed to the criminal legal system, hopefully upending, or at least, lessening, the death by design in US penal institutions:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787443

Until late October, the problem in many African nations “was that we just didn’t have enough doses”, says Salim Abdool Karim, director of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban. “But we now have adequate amounts of vaccines in most countries,” he says. According to the Africa Centres for Disease Control and Prevention, just 64% of the vaccines supplied to the continent have so far been administered. In South Africa, for example, the number of doses administered each week has fallen to less than one-quarter of doses given at the peak of the vaccination drive in September. This is despite only 44% of adults having been vaccinated with at least one dose.

The calls on social media for more doses from Western countries are perplexing, says Espoir Malembaka, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, who is based in Bukavu, DRC. Four types of vaccine are now available in eastern DRC, “but we don’t see people really in a rush to get the vaccine”, except for travellers getting ready to board flights, says Malembaka. He believes that the problem is not access to, but mistrust of, the vaccines. Researchers say that countries might be struggling to get vaccines into arms for many reasons — some of which have nothing to with hesitancy — including poorly funded health-care systems, the fact that doses are often close to their expiry dates and logistical issues getting vaccines to remote regions. But people’s

Studies have attempted to estimate the extent of hesitancy worldwide. One survey of nearly 45,000 participants in 12 countries — conducted before COVID-19 vaccines started being rolled out, and published in July — found that hesitancy was lower in the 10 low- and middle-income nations than in Russia and the United States. But researchers say that the situation has changed throughout the pandemic. In Nepal, for example, where the study found acceptance was highest (97%), the pace of vaccination has slowed, despite only 40% of adults having received one dose:

https://www.nature.com/articles/d41586-021-01987-9

Another survey2 of almost 27,000 people in 32 countries conducted from October to December 2020 found that people’s intentions varied considerably, with high levels of hesitancy in some developing nations. At the extreme, 43% of respondents in Lebanon said they definitely would not be vaccinated.

Another survey of a few thousand people observed even lower acceptance in Papua New Guinea, where only 3% of people have been vaccinated. Researchers found that more than 80% were not planning on getting vaccinated or were uncertain:

https://documents1.worldbank.org/curated/en/293831636115205584/pdf/Addressing-Vaccine-Hesitancy-Survey-and-Experimental-Evidence-from-Papua-New-Guinea.pdf

Some reasons for hesitancy are shared globally, but there are also local differences. A major concern is safety, especially because the vaccines were developed and delivered rapidly and the recommendations for their use have often changed, say researchers. Trust in governments is a related concern. The 32-country survey found that a belief that a government was handling the pandemic well was associated with higher acceptance of vaccines. Another analysis found that increased trust in medical and scientific authorities made people more likely to agree to vaccination. The spread of inaccurate information has also hampered roll-outs in some developing nations. “Misinformation in many places is outpacing evidence-based information,” says Limaye.

But local differences also influence people’s views. In the eastern DRC, for example, decades of war and devastating Ebola outbreaks have fuelled distrust in the leadership and in products from the West, says Malembaka. He also found, in a recent unpublished survey, that COVID-19 vaccine hesitancy might have spilled over to affect people’s willingness to accept other vaccines. Global vaccine inequity might have also contributed to hesitancy, because of “how we’re distributing vaccines to the global south”, says Limaye. "It’s sort of like, here’s our leftovers, they expire in a week.” There are ways to overcome hesitancy, say researchers. Abdool Karim argues that South Africa has hit the point at which people need incentives or even government mandates to get vaccinated. In a recent survey of people in a number of countries, Lazarus and his colleagues found that mandates, such as requiring vaccination to travel by air or attend a workplace, could help to sway decisions. It found that, among people who were hesitant about COVID-19 vaccines, one-third said they would get vaccinated if they had to so that they could travel internationally. Some say the South African government should take lessons from HIV epidemic and engage directly with communities to persuade them, instead of investing in mass-media campaigns. Opportunities to be vaccinated should also be integrated into existing services for the treatment and prevention of other infectious diseases, such as tuberculosis screening or distribution of HIV medications, which are accessible and familiar to people.

Immunisation prevents 4 to 5 million deaths annually, primarily among children, but each year 20 million infants do not receive a full course of the most essential basic vaccines. COVID-19 has underscored the importance of vaccines to public health, but immunisation coverage dropped in 2020 as a result of the pandemic, leaving even more infants un- or under-immunized. The push to manufacture COVID-19 vaccines has raised concerns that supplies of other essential vaccines may be compromised, which could erode the gains achieved by immunisation and delay access for underserved populations. Drawing on data assembled by the WHO and on the advice of technical experts a group describe how COVID-19 is affecting the global supply of key infant and adolescent vaccines (see the table below).

Prior to the pandemic, approximately 5 billion doses of vaccines were manufactured globally each year. In 2022, COVID-19 vaccine production is projected to reach at least 14 billion doses per year. This unprecedented fourfold increase in overall manufacturing is affecting production of essential non-COVID vaccines in several ways. Manufacturers report that they are facing difficulties in timely access to consumable components such as bioprocessing bags, filters, tubing, and laboratory supplies. Culture media—an essential raw material for most vaccines—and vials, syringes, and ampoules have been backordered, with promised delivery times as long as 18 months. Several of those shortages are expected to persist for a considerable time.

These input material shortages are due to the rapid scale-up of COVID-19 vaccine manufacturing, exacerbated by distribution challenges. Because suppliers for certain critical components are limited in number and concentrated in a few countries, access was difficult early in the pandemic when goods distribution was greatly constrained. In addition, emergency measures may have contributed to prioritizing the manufacture of COVID-19 vaccines over the manufacture of other products.

Multiple factors are magnifying the impact of these shortages. Vaccine manufacturers have moved toward lean supply chains, limiting their reserve stocks of input materials and becoming more sensitive to supply disruptions. Manufacturers have also shifted away from stainless-steel bioreactors to single-use assemblies and bioprocessing bags. As a result, they are critically dependent on sophisticated consumable components that are typically not interchangeable.

Some manufacturers report that they have repurposed facilities or production capacity built for other vaccines to manufacture COVID-19 vaccines. In some instances, capacity expansion for non–COVID-19 vaccines has been hampered by delays in equipment availability and installation, with lead times of up to 18 months. Contract manufacturing organisations (CMOs) have limited availability to address capacity constraints for other vaccines because they are being used extensively for COVID-19 vaccine production.

Human resources are also limited. Reassignment to COVID-19 vaccine production and testing, facility lockdowns, and absences due to quarantines and illnesses have caused shortages of experienced personnel, including laboratory staff and engineers. These shortages have delayed some manufacture, testing, and release of essential vaccines and continue to constrain capacity. To monitor product quality, some regulators require submission of every vaccine lot for review and release. This process has been slowed owing to the increased workload for regulatory agencies and because COVID-19 vaccines have been prioritized for regulatory review, delaying the availability of other vaccines. Updates to the manufacturing or testing for vaccines that are already licensed also require regulatory review and may be delayed for similar reasons. Regulatory delays have also been a bottleneck for countries that import vaccines.

More broadly, manufacturers are reevaluating their product portfolios; this may result in reprioritisation or even discontinuation of less profitable vaccines in favour of COVID-19 vaccine manufacture. Vaccines with lower prices and smaller market shares, such as polysaccharide vaccines for pneumococcus and meningococcus, are at greater risk.

Supply disruptions have occurred for pneumococcal conjugate vaccines, measles-containing vaccines, diphtheria and tetanus-containing vaccines, and inactivated poliovirus vaccines. Disruptions have included delivery delays and reduced quantities of specific products (see the table). In most cases, manufacturers have been able to secure stocks of input materials and procurement agencies have been able to access alternative sources, minimizing the impact on vaccination programs. In the latter part of 2021, consumables and single-use materials such as bioprocessing bags remain difficult to obtain. If this leads to vaccine shortages, countries may find it more difficult to close immunity gaps, increasing the potential for outbreaks of measles and other vaccine-preventable diseases:

Products in clinical development, such as human immunodeficiency virus vaccines and next-generation human papillomavirus, tuberculosis, and diphtheria- and tetanus-containing vaccines, are currently delayed or at risk of delay owing to disruptions in the manufacture of clinical materials, the conduct of clinical studies, or regulatory review.

Mitigation Strategies

The group propose actions to reduce the impact of current disruptions and minimize the risks of future interruptions in vaccine supply.

Enabling access to input materials: Access to input materials can be improved by reducing trade barriers to accelerate the flow of goods. The COVID-19 Vaccines Global Access (COVAX) Manufacturing Taskforce has developed the first virtual marketplace to match suppliers of critical input materials with manufacturers of vaccines. Approaches to enabling the flow of these and other materials include using market information to identify specific materials that require expedited customs processing; removing import and export tariffs and other barriers to trade; implementing harmonized coding on critical consumables to expedite their cross-border processing ; and eliminating export restrictions and prohibitions on critical input materials, as called for by leaders of the World Trade Organisation and other international bodies. Such mechanisms are being used to facilitate access to COVID-19 vaccines. Extending them to the overall flow of input materials would help ensure supplies of other important vaccines.

Enhancing regulatory capacity and efficiency: Regulators must ensure vaccine safety and efficacy without loss of time . This will require a combination of greater resources for regulatory authorities and more efficient regulatory processes. As demonstrated in the response to COVID-19, harmonizing processes and expectations across different regulatory bodies, acceptance by one regulatory body of decisions made by another (referred to as “reliance”), and eliminating delays between successive phases of review can drastically accelerate timelines without sacrificing diligence and rigor. These practices can be applied more broadly for other essential vaccines. In addition, streamlined regulatory processes for allowing manufacturers to use functionally equivalent input materials, such as stoppers of different colours, would enable more nimble procurement during shortages.

 

Compiling and disseminating global demand forecasts for essential non-COVID vaccines: Manufacturers rely on demand forecasts for planning and to optimize their use of manufacturing capacity. Through the efforts of WHO, the Pan-American Health Organisation Revolving Fund, UNICEF, and Gavi, the Vaccine Alliance, this kind of market information has become more widely available in recent years. Now, as vaccine supplies and health systems are stretched thin and the context is evolving rapidly, it is even more important to keep abreast of sudden, large changes in demand. This is especially true for vaccines at risk for disruptions (see the table); vaccines at risk of shortages because supply and demand are too closely matched; and for vaccines with a potential for demand surges, such as those used in outbreak response. We suggest that comprehensive, global demand forecasts should be compiled more frequently and that more countries should contribute high-quality demand data for the sake of forecasting.

Enabling demand flexibility: Vaccine procurement specifications typically limit the range of products that can be purchased. They may require specific product presentations (such as multidose vials or prefilled syringes), suppliers of particular nationalities, or products and labelling that have been approved by the local regulatory authorities . Where global policy and regulatory recommendations support the use of similar vaccines made by different manufacturers, greater flexibility in product choice and procurement could enhance access. Such flexibility may require acceptance of a product addressing fewer strains, or use of reliance mechanisms, including WHO prequalification (which enables procurement by United Nations agencies) , that can expedite marketing authorisation. Further regulatory convergence on simplified, harmonized labels acceptable across many jurisdictions would increase flexibility in procurement.

Healthy markets for vaccines provide reliable, timely supplies of high-quality vaccines at sustainable prices and enable innovation to meet evolving needs. Although COVID-19 has posed new risks in the short term, it has also driven several changes that may create opportunities for long-term improvements in market health. First, once demand for COVID-19 vaccines is met, manufacturers and CMOs will be left with a legacy of much higher capacity. Although some downsizing is anticipated, there will also be opportunities to repurpose this capacity to address existing shortages; support the development and manufacture of new vaccines or other biomedical products; or maintain existing manufacturing capacity in a state of readiness to respond to future emergencies. Leveraging this capacity will require a willingness to invest in being better prepared for the next pandemic.

Second, challenges in global access to COVID-19 vaccines have led to calls for the global diversification of vaccine manufacturing. Increasing manufacturing capacity in underserved regions would accelerate regional access to vaccines and improve preparedness and rapid response for future emergencies.

Third, newer vaccine platforms such as nucleic acid and viral-vectored vaccines are showing their flexibility and utility in the response to the COVID-19 pandemic. These new platforms can drastically accelerate adaptation to new pandemic and seasonal influenza strains; could be applied to additional pathogens, accelerating access to new vaccines; and could potentially be used in curative applications—for example, as cancer vaccines. Finally, the mitigation strategies discussed above will yield a more efficient and resilient vaccine manufacturing ecosystem. In future pandemics, this ecosystem will better enable rapid, equitable access to pandemic vaccines and ensure reliable supplies of other essential vaccines.

The global response to the COVID-19 pandemic has demonstrated the power of vaccines to fight disease and the power of global collaboration to achieve unprecedented speed and scale in the discovery, manufacture, and delivery of new vaccines. It has also shown the importance of equitable access to vaccines and of resilient health systems that can deliver routine care, including vaccination, while coping with health emergencies.

At the same time, COVID-19 is creating challenges for other vaccines. Disruptions in the supply of essential infant and adolescent vaccines will disproportionately affect poorer countries, which are at greater risk of disease.

Owing to complex manufacturing processes and long production times, manufacturing constraints are typically slow to show their full impact, with a delay sometimes up to 12 to 18 months. Similarly, actions taken may not result in increased supplies for over a year. It is therefore critical to identify and mitigate risks to vaccine supplies as early as possible to minimize their impact.

Mitigating those risks requires a strong, pre-emptive, and coordinated effort. The measures proposed in this paper build on innovative collaborations underway to accelerate access to COVID-19 vaccines. Expanding their scope will help ensure reliable supplies of all essential vaccines. Moreover, applying these mechanisms more broadly will contribute to healthier vaccine markets that are better prepared to respond to future emergencies.

The actions described here are needed to enable recovery, extend the benefits of immunisation to underserved populations, and speed the introduction of new vaccines, contributing to a healthier, safer, and more prosperous future.

The response to the COVID-19 pandemic in the has been transformed through new technologies. The speed of progress in combatting this pathogen has outpaced the advances made against perhaps any similar public health threat over any comparable period. The rapid introduction of highly effective vaccines, the development of monoclonal antibody drugs and most recently, antivirals that are taken orally have offered a potent armamentarium to reduce the adverse effects of SARS-CoV-2 infection. Perhaps one of the most enduring technological innovations will be the advent of accurate diagnostic tests that can be used at home to provide a rapid answer about a person’s clinical status. As a result of the regulatory framework fashioned to advance these tests, the technology and commercial pathway to provide them directly to consumers, and the cultural change they have ushered in, our approach to care will have lasting consequences beyond COVID-19 and to how we address other infectious diseases.

In the future, home diagnostic tests will be increasingly coupled with telemedicine visits to introduce rapid assessment into the home for a range of pathogens, such as group A Streptococcus, influenza virus, respiratory syncytial virus, and many more. These virtual visits will be tethered to more definitive diagnostic tests, such as polymerase chain reaction, with delivery of such test kits to a patient’s home and same-day return to the laboratory for conclusive confirmation that a negative test result from an at-home, rapid diagnostic device was not a false-negative result.

This ability to connect at-home diagnostic tests with telemedicine and rapid turnaround of definitive laboratory testing will change infectious disease management. These systems will reduce office visits that can risk the spread of disease to others, make rapid assessment and treatment more possible, and expand access to timely, more affordable medical care. As the leadership of the US FDA medical device program said, “lessons learned from our experiences with COVID-19 could be leveraged to facilitate a large-scale effort for swift, widespread access to accurate and reliable tests for a variety of diseases. They can also inform the response to a future public health emergency.”

The significance of the innovative policy changes at the FDA in facilitating at-home diagnostics cannot be overstated. It represents a watershed moment in the FDA’s approach to regulation.

In fostering these opportunities to address COVID-19, the FDA addressed many practical challenges, including a streamlined approach to test development and evaluation. For example, the FDA’s adoption of submission templates decreased development uncertainty and burdens on test developers. The issues addressed by the agency went beyond the technical evaluation of the performance characteristics of the devices to encompass how the tests would be used in a novel approach to treatment and in the setting of a public health emergency.3 Key among these challenges was how to collect positive test results for a reportable pathogen like SARS-CoV-2 and how to make sure that patients had access to appropriate follow-up care. In enabling access to at-home COVID-19 tests, the FDA relied on labeling and guidance to consumers, recognizing that the imperative to expand access to testing offset the reality that many positive test results would go unreported and that some patients may not take appropriate actions based on the test findings. The FDA provided a path for developers to build technological solutions into tests or to offer tests that were coupled to services—for example, downloadable apps to visualize and report results—and link them to telehealth services.

Continued advances in technology will expand these opportunities. The FDA has identified accurate molecular tests, breath analyzers, and light-based devices as platforms that can be placed in homes to screen for a range of pathogens, perhaps through interchangeable modules tailored to different tasks. Once these platforms are deployed to homes, they can be used in future public health emergencies as well as for routine clinical applications. Officials at the FDA have noted that “in general, it is easier to add a new, specific target of analysis to an existing platform than it is to create, validate, and manufacture an entirely new test and testing platform.”

This adaptability is especially relevant to at-home tests because they often undergo additional validation by the FDA to demonstrate accuracy and reliability in the hands of untrained users. The agency recognized that adopting platforms that can be used for testing across a range of pathogens enables these upfront validation steps to be done once with the initial evaluation. The FDA has noted that this work can then be leveraged for future assays that can be run on the same platforms and users can utilize the same tools and follow similar procedures in the same basic testing steps while screening for different pathogens. Deploying standardized technologies can help advance routine clinical care and leave the country on a stronger footing in the event of future pandemics. Existing platforms could be leveraged to quickly make point-of-care and at-home testing more widely available. Developing these technologies, and encouraging their adoption, can inform the response to a public health emergency and thus should be a part of the nation’s future pandemic planning.3

Platforms with many of these characteristics are already in use. Some COVID-19 test developers have created devices for at-home molecular screening that could be used with interchangeable cartridges that, in the future, will enable testing for other viral pathogens on the same device. The familiarisation that has taken place through consumer use of these devices creates opportunities for new approaches in how we address infectious disease. But challenges remain, and realizing these goals will require other changes beyond the regulatory review of these products. Chief among them is how we offset the cost of these opportunities for consumers.

Many US consumers were locked out of the opportunity to use at-home tests for COVID-19, especially for routine and serial testing for which the tests were best suited. For many people, the tests were not affordable or hard to obtain, and policy makers struggled to create policies to directly subsidize their distribution to patients. In Germany, England, South Korea, and other countries, at-home tests were provided for free to consumers as a part of national strategies for confronting the pandemic. Ideally, these tests would be provided in a similar way in the US, and after the public health emergency has passed, perhaps by insurers and employers who recognize the value in offering consumers the opportunity for rapid assessment of infectious diseases and avoiding costlier visits to their physicians that can worsen illness or increase spread in households.

The regulatory pathway outlined by the FDA for the Emergency Use Authorisation of COVID-19 tests has shaped a foundational change in how these tests are developed and deployed in the US. This change creates the opportunity for a dramatic paradigm shift in the practice of medicine. The wide adoption of these testing platforms, coupled with other advances in care, including the widespread use of telemedicine and the participation of companies providing laboratory services directly to the home, represents a significant advance in delivery of medical care. It represents a cultural shift likely to persist long after COVID-19 becomes an endemic illness—and it should—because it offers profound opportunity to improve the affordability, access, and effectiveness of medical care for a range of common diseases:

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2787641

Further snippets:

Researchers asked what is the association between COVID-19 testing and case rates on residential college campuses? In this cohort study of 18 Connecticut colleges and universities, infrequent COVID-19 testing of residential students was not associated with decreased transmission, whereas testing of residential students twice per week was associated with decreased transmission during the 2020-2021 academic year. Findings suggest that twice-weekly COVID-19 testing of residential students may serve as an effective infection mitigation strategy at colleges and universities:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787433

Next, can telemedicine be used to differentially diagnose unilateral sudden hearing loss (SHL)? This cohort study comprised 51 patients with unilateral SHL evaluated with a telemedicine model that included self-performed Weber tests and app-based audiometry. The model’s sensitivity, specificity, and accuracy for diagnosing sudden sensorineural hearing loss (SSNHL), defined as acute loss of 30 db or more in 3 or more consecutive frequencies, were 100%, 73.3%, and 84.3%, respectively. Telemedicine may serve as a reliable primary tool for identifying patients with SSNHL who are in need of an urgent care but are remote from medical resources, especially during this era of COVID-19 pandemic:

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2787502

Researchers now report the results of a double-blind, randomised, placebo-controlled, endpoint-case driven, phase 3, clinical trial of a single dose of an adenovirus type 5 vectored vaccine (CanSino Biologics, Tianjin, China) in adults 18 years and older. The study involved 18,363 vaccinated and 18,354 unvaccinated participants from Argentina, Chile, Mexico, Pakistan, and Russia, with recruitment beginning in September, 2020, and continuing until the endpoint of 150 COVID-19 cases was reached in January, 2021. The racially diverse study cohort was approximately 70% male, and approximately 20% of the participants were aged 45–59 years and approximately 8% were 60 years or older. The primary endpoints were efficacy and safety, with efficacy being measured by the prevention of symptomatic, PCR-confirmed SARS-CoV-2 infection 1 month after vaccination and safety measured by the incidence of severe adverse events. Vaccine efficacy in preventing symptomatic disease 14 days after vaccination and in preventing severe COVID-19 served as secondary efficacy endpoints. 28 days after vaccination, Efficacy against PCR-confirmed COVID-19 was 57·5% (95% CI 39·7–70·0; p=0·0026) and 91·7% (95% CI 36·1–98·9) against severe COVID-19. Similar efficacy numbers have been reported in clinical trials of the Oxford AstraZeneca chimpanzee adenovirus vectored vaccine (62·1% in recipients of the standard dose) and the Jansen, Johnson & Johnson adenovirus type 26 vectored vaccine (66·9% against COVID-19 and 76·7% against severe COVID-19).  In terms of safety, the authors reported the expected range of systemic and local reactions (fever, headache, and muscle aches, as well as redness, swelling, and pain at the injection site). Serious adverse events were relatively rare, and the rates did not differ between vaccine and placebo groups. Given differences in the timing, geographical region, study cohorts, and circulating variants, these three vaccines appear to have broadly similar safety and efficacy profiles. Most previous phase 3 clinical trials of COVID-19 vaccines have found that there is a lag period of roughly 14 days between vaccination and the start of protection. They report a similar lag period of approximately 12 days:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02834-8/fulltext

Although the reported efficacy was slightly higher at 14 days (63·7% [95% CI 52·9 to 72·1]) than at 28 days post-vaccination, the CIs overlap and no formal analysis comparing the efficacy rates was done. It is also noteworthy that efficacy was substantially lower (17·5% [95% CI –127·6 to 70·1]) in participants aged 60 years and older than participants younger than 60 years, suggesting that additional vaccine doses might be necessary in this age group. The study has multiple strengths including the large cohort size of over 18,000 vaccine recipients; the global nature of the study, with recruitment sites in multiple countries allowing for greater racial and ethnic diversity; the inclusion of older adults (aged > 60 years); the clear definitions of COVID-19 and severe COVID-19; and weekly contact with participants to actively identify cases and retain a high participant retention. These strengths increase the reliability of the findings. As with most clinical trials, individuals with compromised immune systems, unstable medical conditions, and other potential risk were excluded and we will need to wait until real-world effectiveness studies are done to ascertain the ability of the vaccine to provide protection in these vulnerable groups. I note women made up less than a third too:

Researchers in Israel prospectively assessed the safety and immunogenicity of the booster dose, 1 month after its administration, in a cohort of 72 actively treated patients with cancer, compared with a matched group of 144 healthy individuals. Before booster administration, 20 (28%) patients with cancer were found to be seronegative, compared with only two (1%) of the healthy individuals (p<0·0001). After administration of the booster, three patients with cancer and none of the healthy individuals remained seronegative. A significant increase in anti-SARS-CoV-2S IgG absolute antibodies concentrations in both groups was also noted (p<0·0001 for the comparison of pre-booster and post-booster concentrations within each group). Yet, higher pre-booster and post-booster antibody concentrations were noted in healthy individuals than in patients with cancer (p=0·00011). Multivariate analysis, including study group (patient or control) and time (before or after third dose) adjusted for the matching factors (age and gender) indicated that the only statistically significant variable associated with increased titre levels was administration of the booster (p<0·0001):

Above shows SARS-CoV-2 S IgG antibody values in serum samples of actively treated patients with cancer (n=72) and healthy controls (n=144) before (blue circles dots) and after (red squares) the third dose of BNT162b2 vaccine.

These data suggest a high rate of waning immunogenicity in patients with cancer approximately 6 months after the administration of the second dose of BNT162b2, and support the use of a booster dose in this vulnerable population of actively treated patients with cancer. The modest side-effect profile further supports this recommendation. Although the study cohort was relatively small, they believe that the explicit data from this population, combined with the robustness of the national data, support the recommendation for a third dose booster for actively treated patients with cancer.

Graphs:

Emerging hot spots in the US. The x-axis is growth rate of new cases compared to last week, the y-axis is the new case per hundred, and z is the latitude. Each state is colour coded by vaccination rate:

Justin Stebbing

Managing Director

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