provider relief funding.9 In the fall of 2020, MACPAC interviewed Medicaid officials in five states and representatives from national provider organizations for pediatricians, HCBS, and behavioral health providers to learn more about the barriers experienced by Medicaid providers applying for provider relief funding. Stakeholders noted that some providers did not apply because they were not aware they were eligible and were confused about how the provider relief fund related to other forms of COVID-19 relief funding, such as the paycheck protection program and Medicaid retainer payments for HCBS providers. Also, stakeholders noted that the application process was burdensome, especially for small providers with few administrative staff and for Medicaid providers who were not included in HHS’s list of potentially eligible providers curated by state Medicaid and CHIP agencies and had to follow a special exceptions process to prove that they were eligible COVID-19 therapeutics: Challenges and directions for the future The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the next pandemic challenge and to allow rapid and cost-effective development of new therapeutics with equitable delivery.From the outset, COVID-19 has been an infection with significant mortality. As the pandemic swept across the world, we urgently needed to determine effective and optimal therapies for patients at each stage of disease. However, as a novel virus, there was very little information to guide choice of therapy and considerable debate about which agents to include in clinical trials.The enormity of the pandemic has led to a welcome focus on collecting only that information which informs decision making in clinical trials, but also to a plethora of trials that did not collect information on enough patients to be truly informative. Therapeutic strategy has been lacking; some potential therapies have been tested multiple times (e.g., >150 hydroxychloroquine trials), while other promising approaches have yet to be tested at scale (e.g., anti–GM-CSF [granulocyte-macrophage colony-stimulating factor], anti-TNF [tumor necrosis factor]). Future efforts need to be more coordinated without stifling innovation.Ideal COVID-19 treatments are inexpensive, with a good safety profile, and prevent clinical deterioration and hospitalization. Currently, the only therapies with published evidence of benefits early in the course of infection are inhaled interferon (IFN), small molecules, and monoclonal antibodies (mAbs). All are expensive, with limited availability and, hence, are impractical for the majority of the world’s population. We also have a limited understanding of on whom to focus early treatment. Age, obesity, diabetes, hypertension, and immune compromise increase the likelihood of clinical deterioration, but we need biomarkers to better predict progression. For patients in hospitals, there are approved therapies that are effective in a subset of severe cases—namely dexamethasone, tocilizumab, and remdesivir—but again the costs of the latter two are prohibitive for most countries. It is clear that we need cost-effective drugs that prevent disease progression and are easy to administer in all countries, including low- and middle-income countries.Here we review all aspects of COVID-19 therapeutics. We explore challenges that have stymied COVID-19 drug development and highlight important unmet needs. We examine key therapeutic classes and identify promising novel approaches for the current and future pandemics. Therapeutic strategy is always controversial and we recognize that the opinions expressed here will not meet with universal agreement, but we have endeavored to be inclusive in our assessment.Pandemics stress the clinical trial process and conventional trial set-up processes are too slow for a rapidly spreading pathogen. Prepandemic clinical trial networks demonstrated their value by enabling rapid recruitment, such as with Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) (1) in intensive care unit (ICU) patients. In contrast, for non-ICU hospitalized or primary care patients, there was no established framework. In these key populations, early drug development was characterized by small, underpowered clinical studies of repurposed