key: cord-0796574-xm9kx5gz
authors: Carter, Jessica; Friedland, Jon S.; Kirwan, Daniela E.; Nathavitharana, Ruvandhi R.
title: Translating scientific discoveries during pandemics: ensuring equity for people affected by COVID-19 and tuberculosis
date: 2020-10-19
journal: ERJ Open Res
DOI: 10.1183/23120541.00562-2020
sha: c3d206a553d9ac344e5769cd61719a451ee62b45
doc_id: 796574
cord_uid: xm9kx5gz

The #COVID19 pandemic has emphasised major global health inequities: this editorial argues lessons learnt from TB must remind us of the gaps in the research agenda that must be addressed to ensure that scientific advances are equitably disseminated https://bit.ly/3bTZHS3

Currently much of the focus of COVID-19 research is on treatment for hospitalised patients, often those in intensive care, not in the community where most COVID-19 patients are found. Exceptions include the UK PRINCIPLE (Platform randomised trial of interventions against COVID-19 in older people) trial, which seeks to evaluate treatments that could prevent hospitalisation in people over 50 years of age [7] . Lessons can be learned from the decentralisation of TB care, which seeks to promote earlier diagnosis and treatment to decrease transmission and reduce the need for hospital-based care [8] . Research focused on the development and implementation of community-based strategies, including social distancing and the use of facemasks [9] , for COVID-19 prevention and mitigation is urgently needed, given that health systems in many countries have become overwhelmed to the point of collapse.

In contrast to TB, there has been rapid progress to develop and obtain emergency use authorisations for COVID-19 tests. Yet, similarly to the challenges of interpreting immunological assays for latent TB infection or understanding the negative predictive value of tests such as smear microscopy or urine lipoarabinomannan for TB disease [10] , COVID-19 testing has raised questions regarding the sensitivity and duration of positivity of molecular tests and the relationship between positive serological testing and lasting immunity [11] . New concepts have been proposed including "immunity passports", which may be issued to those with detectable antibodies; however, this could negatively impact equity by creating a tiered society, and thus recommendations for serological test interpretation must be clear. While the ability to perform COVID-19 testing using the Gene Xpert platform may facilitate scale-up of COVID-19 testing in high TB incidence countries, challenges encountered during the widespread implementation of Xpert MTB/RIF including gaps in linkage to care, monopolisation by a single diagnostic platform, and reliance on donor support should inform COVID-19 testing strategies [12] .

Drug regulatory agencies such as the US Food and Drug Administration, European Medicines Agency, and UK Medicines and Healthcare products Regulatory Agency have set up COVID-19 treatment acceleration programmes to facilitate the navigation of administrative requirements and expedite review. In contrast, years of TB research underfunding have stifled TB drug development. More than 50 years elapsed between the development of the core drug regimen in the 1950s and the introduction of bedaquiline, the first new antibiotic developed to treat TB in the 21st century [13] . TB treatment has remained lengthy, complex, and toxic, particularly for people with drug-resistant TB [1] .

Although regimens including new and repurposed drugs such as bedaquiline and linezolid are now recommended by the WHO, most patients who would benefit from new TB treatments are not receiving them due to prohibitive costs and delays in regulatory approvals [1, 14, 15] . Early indications that remdesivir may be effective in COVID-19 immediately highlighted similar equity concerns regarding treatment scale-up [16, 17] , despite the substantial contribution of patients from low-resource settings to the clinical trials that were vital to drug development and evaluation [18] . While efforts to ramp up production were underway, Gilead donated its entire supply of remdesivir to the US government. However, the lack of transparency regarding the initial distribution of the drug within the USA received widespread criticism, particularly given its conspicuous absence in major safety net hospitals [19] . This is an important reminder that the global impact of effective new drugs will depend heavily on the speed and approach to scale-up drug production, as well as principles underpinning distribution, in the shifting landscape of heavily affected countries. Voluntary licences with generic drug manufacturers in countries like India may help. In contrast, data from the UK RECOVERY (Randomised Evaluation of COVID-19 Therapy) study indicate that a cheap and widely available drug, dexamethasone, decreases mortality in COVID-19 patients requiring respiratory support [20] . This highlights the important benefit that well-designed, timely clinical trials can provide to patients in both high-and low-income settings, if scale-up is rapid.

Promising early data suggest that recently developed vaccines may induce protection against SARS-CoV-2 [21] . Oxford University has formed a collaboration with AstraZeneca for global development and distribution of the University's potential recombinant adenovirus vaccine, with both partners agreeing to operate on a not-for-profit basis during the pandemic [22] . It remains to be seen how accelerated plans for vaccine testing will be scaled up in low-and middle-income countries. We compare this to TB where there is just one vaccine in clinical use, the bacille Calmette-Guérin (BCG) vaccine, developed in the 1920s and which is of limited effectiveness, compared to the over 150 SARS-CoV-2 vaccines currently in development including 21 in clinical evaluation [23] . Shortages of the BCG vaccine continue to occur [24] and, ironically, media attention surrounding its potential role to prevent COVID-19 may further compromise supplies [25] . Vaccine implementation efforts will also need to address the vaccine hesitancy lobby, which remains resolute despite the universal risks of COVID-19 [26] .

Analyses from UK data demonstrate that COVID-19 mortality is disproportionately higher in Black, Asian and Minority Ethnic groups, which is likely driven by unequal social determinants of health, including the occupational risks of serving as essential workers [27] . While urgent efforts are needed to tackle structural racism as a health issue, researchers must simultaneously ensure representation of affected communities in study populations. We know that those living near university-affiliated hospitals are more likely to be enrolled into clinical trials, leaving minorities, rural communities, and countries without links to established academic institutions at risk of being left behind [28] . The WHO has taken positive action through launching the SOLIDARITY trial which has over 90 countries participating, but more active steps to include marginalised populations are needed [29] . Successful interventions should be produced at scale and distributed according to need, not wealth.

The WHO's Alma-Ata declaration in 1978 stated that gross health inequalities are unacceptable. The COVID-19 pandemic emphasises the disproportionate burden of emerging threats faced by communities already suffering from major health inequities. Despite efforts by the USA to withdraw funding from the WHO, the need for a coordinated global public health response is more apparent than ever. Although COVID-19 has captured public and political attention in a way that TB has consistently failed to achieve, our experience with TB serves to remind us of the gaps in the research agenda that must be addressed to ensure that scientific advances are equitably disseminated (table 1) . Unfortunately, as in TB, mistrust of governments and health systems is likely to compromise the COVID-19 response [30] . Consistent and clear scientific and political communication with the public can help to ensure the success of public health efforts. Interventions should not be executed in a one-size-fits-all manner, but should be adapted based on community needs and seek to mitigate social injustices. The response to COVID-19 has shown us that fast-track research, collaboration, data sharing, and rapid increases in funding to address global health crises are possible. We argue that these innovations must also be made available to those working to defeat TB and other public health threats, as part of long-term, sustainable strategies to ensure that all members of the global community benefit from scientific advances. This will require strong political leadership, and a commitment to the WHO's stated goal of Health for All. 

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