A National Strategy for COVID-19 Medical Countermeasures: Vaccines and Therapeutics

The US needs a strategy for a “new normal” of living that includes COVID-19. This “new normal” will occur when total respiratory viral infections, hospitalizations, and deaths inclusive of those from COVID-19 are no higher than what typically occurred in the most severe influenza years before the current pandemic. Integral to achieving and sustaining this “new normal” are both faster development and more efficient deployment of vaccines and therapeutics. While COVID-19 has ushered in new vaccine platforms, repurposed existing therapies, and stimulated rapid development of monoclonal antibody and oral antiviral treatments in record time, much remains to be done to ensure these life-saving medicines are accessible to all.

Even without population-wide coverage, COVID-19 vaccines have significantly reduced the number of disease-related hospitalizations and deaths from SARS-CoV-2 in the US. For instance, states with higher vaccination rates have lower hospitalizations and deaths.¹ But given the continuing rates of hospitalization and mortality from COVID-19, more needs to be done.

To minimize the effects of COVID-19 on daily life and return to normalcy, some estimates suggest that 90% or more of individuals in the US are likely to need some immunity to SARS-CoV-2, whether from vaccination or prior infection.² Nine of 10 Organisation for Economic Co-operation and Development countries with full vaccination rates greater than 75% have neared or exceeded the target of less than 1 COVID-19 death per 100 000.³ In January 2022, approximately 60% of the US population has been vaccinated.

COVID-19 vaccines authorized or licensed by the Food and Drug Administration (FDA) include 2-dose mRNA vaccines and a single-dose adenovirus-vectored vaccine, with additional doses recommended for older adults and immunocompromised persons. In November 2021, the Centers for Disease Control and Prevention recommended people 18 years and older receive an additional vaccine dose 6 months after the last vaccination with a goal of reducing overall infections and, perhaps, transmission rates. Preliminary findings show boosters are more effective in neutralizing the Omicron variant compared with a 2-dose mRNA regimen, although early indications suggest this effect may not be sustained. Early data suggest immunity from prior infection is insufficient to neutralize the Omicron variant, but is likely to protect against severe disease and death. Immunological responses vary among individuals. Unless SARS-CoV-2 evolves to become more attenuated than its current form, the nation should anticipate needing regular, possibly annual, COVID-19 vaccines. It is still unclear at what point protection against severe disease will wane. As with yearly influenza vaccines, an updated formulation targeted to the circulating variants will likely be needed to maximize protection from infections and severe disease.

Achieving 90% population vaccination coverage will require mandates. Few countries have ever achieved such levels of coverage of any vaccine without vaccination requirements. Mandates have been shown to be effective, especially among individuals who are not fundamentally opposed to vaccination, but are procrastinating, confused, or have barriers to access. Thus, proposed vaccine requirements for government employees and contractors, health care and long-term care workers, and employees of businesses with 100 or more employees will be necessary to achieve levels of coverage to return to pre–COVID-19 life expectancy and social and economic vitality. For example, as New York City has done, such a requirement may need to be expanded to include all workplaces. Additional requirements for consideration may include vaccination for public transportation and indoor events, with proof of a recent negative SARS-CoV-2 test for those who are not vaccinated.

Once analysis of a large pool of vaccinated children determines that the risk-benefit profile of COVID-19 vaccines is completed and vaccines are licensed, vaccination should be required for school attendance. Vaccination requirements must be paired with appropriate paid sick and family leave for parents and adult workers to accommodate recovery from reactions to the vaccine.

To reduce virus transmission and infections, next-generation COVID-19 vaccines that match circulating SARS-CoV-2 variants need to be deployed. Genomic surveillance coupled with nimble vaccine technology allow for rapidly adapting vaccines to emerging variants. The FDA has indicated a pathway to implement a rapid, strain-change regulatory process with a minimal amount of clinical data, a review process similar to that applied to seasonal influenza vaccines. Over the next few months, vaccines specific to circulating variants should be phased-in. The vaccine manufacturers and FDA should work expeditiously to ensure the prompt submission of data and their review.

In addition, the government needs to facilitate further development of vaccines, including alternate dosing and administration approaches. Despite COVID-19 vaccines being authorized for more than 12 months, there is insufficient data on what constitutes an optimal vaccine combination and schedule. Is there a more effective prime/boost regimen when combining mRNA, viral-vectored, or protein vaccines? Is there an optimal dosing interval? Is there a correlate of protection to expedite further vaccine development? The government needs a focused research program to get these answers as soon as possible.

The government should accelerate efforts to develop a universal coronavirus vaccine to protect against known coronaviruses, including SARS-CoV-2.⁴ A more broadly protective vaccine would allow the world to limit the effects of emerging variants and nimbly react to novel coronaviruses that are likely to emerge in the future. There may be tradeoffs between increased breadth of protection against severe disease and reduced effectiveness against infection.

The government needs to invest in and provide a full incentive for innovative approaches to improve vaccine access and uptake globally. Some examples include mucosal vaccines that may offer greater protection from infection and skin patches that decrease the complex logistical challenges of vaccination campaigns, such as cold chain delivery. These approaches will reduce supply chain constraints and deployment logistics while reducing the overall cost of vaccinations globally.

In addition, to facilitate verification of vaccination status and to better track postvaccination infections, there needs to be an electronic vaccine certificate platform. Relying on forgeable paper cards is unacceptable in the 21st century. Current state immunization information systems are incomplete, fragmented, and not interoperable, hindering national efforts to control the virus. A national electronic vaccine certificate platform is needed, such as the SMART Health Card, that ensures interoperability across states and countries, safeguards individual privacy, and is based on open-source technology publicly available for vetting to help satisfy any concerns over government surveillance. While controversial, this is not unprecedented. State and national databases are in use for other information, including for driver’s licenses, Social Security, voter registration, and specific health purposes, such as organ donation.

Several effective therapeutics for COVID-19 are available, including remdesivir and dexamethasone.⁵ Monoclonal antibodies targeting the virus are highly effective when administered early, but myriad barriers, such as poor coordination between COVID-19 testing sites and the health care system and limited supplies, have limited their utility.⁶ In addition, the Omicron variant has rendered all but one of the monoclonal antibodies essentially ineffective, requiring them to be redesigned to match evolving variants. Host-targeted therapies that can reverse cytokine-induced inflammation should be further explored to rescue patients with late-stage disease.

A more effective response to COVID-19 will require rapid development of efficacious oral antiviral treatments. Molnupiravir and Paxlovid were recently authorized by the FDA. Molnupiravir has a relatively low effectiveness and there are questions about potentially serious adverse effects, such as mutagenicity and birth defects.⁷ Paxlovid, a novel oral protease inhibitor combined with an existing protease inhibitor, seems more effective with fewer safety concerns.⁸ As is the case with monoclonal antibodies, the clinical benefits of these drugs may be limited due to inadequate coordination between testing and treating patients within the health care system and severely limited supply. Further, the use of antiviral agents warrants close monitoring for emergence of viruses resistant to treatment. The US government should accelerate development, production, and procurement of COVID-19 drugs that are easier to manufacture and administer.

Outpatient COVID-19 treatments need to be made widely available at no cost—no deductible, no co-pay, no pay for the uninsured—for anyone testing positive for SARS-CoV-2 infection and meeting FDA indications. Importantly, there must be a mechanism to ensure every person who tests positive is proactively offered appropriate and rapid treatment. If a patient tests positive, whether at home, a pharmacy, or hospital clinic, there must be a mechanism for treatment to be initiated immediately following diagnosis. Certain COVID-19 treatments should also be made more readily available for preexposure prophylaxis in high-risk groups, especially those who do not respond to vaccination.

There has been tremendous progress in rapidly creating novel COVID-19 vaccines and therapeutics. Nevertheless, these efforts have been insufficient to achieve a “new normal,” in which the combined risk of all viral respiratory illnesses, including COVID-19, does not exceed the risk during pre–COVID-19 years. The US needs investment in variant-specific vaccines, alternative vaccine administration mechanisms, and research into the optimal vaccination strategies. Having effective vaccines are of real value in reducing the spread of COVID-19 and serious illness, but their benefits will be limited without near universal coverage. This coverage can be augmented through additional vaccination requirements. Finally, research needs to be expedited to develop and use effective COVID-19 oral therapeutics. The short window for administration requires a much closer linkage between COVID-19 testing and treatment.

Corresponding Author: Ezekiel J. Emanuel, MD, PhD, Perelman School of Medicine, Medical Ethics and Health Policy, University of Pennsylvania, 423 Guardian Dr, Blockley Hall, Ste 1412, Philadelphia, PA 19104 (zemanuel@upenn.edu).

Published Online: January 6, 2022. doi:10.1001/jama.2021.24165

Conflict of Interest Disclosures: Dr Borio reported being a venture partner at Arch Venture Partners, receiving personal fees from Resilience Corp, and serving on the scientific advisory board for the Coalition for Epidemic Preparedness Innovations and on the board of directors for Eagle Pharmaceuticals and Insulet Corp. Dr Emanuel reported personal fees, nonfinancial support, or both from companies, organizations, and professional health care meetings and being a venture partner at Oak HC/FT; a partner at Embedded Healthcare LLC, ReCovery Partners LLC, and COVID-19 Recovery Consulting; and an unpaid board member of Village MD and Oncology Analytics. Dr Emanuel owns no stock in pharmaceutical, medical device companies, or health insurers. No other disclosures were reported.

Additional information: Drs Borio, Bright, and Emanuel were members of the Biden-Harris Transition COVID-19 Advisory Board from November 2020 to January 2021.