COVID-19 will have both short-term and long-term impacts on society—many of which we’re already seeing today. With the number of cases multiplying, healthcare systems are being pushed to their limits, the global supply of personal protective equipment (PPE) has been disrupted, large events and public spaces have been shut down, and the economy is suffering. Additionally, communities are struggling to adjust to their “new normal” of home schooling, work from home, and social distancing.
While much is still uncertain, there is also hopeful news. More than 160 drugs are already in development or being repurposed to treat those infected with COVID-19, and groups around the world are hard at work on several potential vaccines for the virus.
What role will successful treatments and effective vaccines play in controlling COVID-19 in the future?
Of the 7.8 billion people on the planet, approximately 3 million people have been confirmed COVID-19 positive. That means roughly only 0.038% of the global population potentially has natural immunity. This estimate excludes individuals with mild to moderate symptoms who go untested, which represents a significantly higher portion of the population. We also don’t know for certain if individuals develop natural protective immunity after infection. Additionally, as many countries start to ease up social distancing measures, the likelihood of a resurgence in disease is high. In fact, we’re already starting to see evidence of a second wave in China. With these factors in mind, it’s apparent that a sustainable, multi-pronged approach with multiple manufacturers for both medications and vaccines is necessary.
COVID-19 varies in severity and progression, which means multiple types of treatments are needed to address the different stages of the illness. Prevention measures can help, but we need wide-scale, inexpensive, and accessible testing to truly get a handle on the current problem.
Effective testing programs allow health authorities to comprehend how prevalent the disease is, as well as how it is evolving. Large-scale testing can rapidly identify which individuals have the disease and need care, as well as individuals who may be asymptomatic and should isolate. Isolation of known cases prevents infected individuals from coming into contact with others, thus slowing the rate of transmission.
As for vaccines, multiple approaches are currently under investigation. It’s likely we will see a variety of vaccines licensed, which will be critical in addressing global supply and reaching protection levels high enough to achieve some level of herd immunity.
How will vaccines help control the spread of COVID-19?
First, we must consider the large number of undiagnosed, asymptomatic, and mildly ill people who would not think to seek treatment or take more precautionary measures because they don’t feel sick. These individuals have the potential to unknowingly spread the disease to others, sometimes even becoming what is known as “super spreaders.” A good example of this is the case of “Patient 31”—a mildly symptomatic patient in South Korea who visited a hospital, church, and hotel and is linked to hundreds of cases in the country. The best way to prevent this phenomenon is to stop individuals from getting infected in the first place through vaccination.
It’s also important to consider the pressure placed on the global medical community. COVID-19 has already shown cracks in the system, from the lack of ventilators and PPE for front line medical workers to the physical toll on healthcare providers, many of whom have lost their lives fighting this disease. These challenges are further amplified in underserved communities where individuals often lack access to the most basic aspects of healthcare and healthcare systems are ill-equipped to deal with a pandemic. In these areas, disease is likely to spread more rapidly due to cramped living conditions, inadequate sanitization, and the lack of necessary medical interventions.
Typically, vaccine development is an expensive and lengthy process. However, candidates for a COVID-19 vaccine are progressing faster than that for any other pathogen in history. Vaccine manufacturers are exploring many different approaches, including:
- Inactivated: This is a straight-forward technology with existing infrastructure used for several licensed human vaccines. Inactivated vaccines are usually safe for use in many populations, including immunocompromised individuals and pregnant women.
- Live Attenuated: These are typically one-dose vaccines that produce a great immune response which would be ideal for the current outbreak setting.
- Intranasal: This uses a less invasive mode of vaccine administration (through the nose instead of an injection), making it more patient-friendly.
- DNA: This innovative technology has a relatively low production cost, is easy to scale up, and rapid vaccine production is possible—again making it ideal for this ongoing pandemic.
- mRNA: Similar to DNA vaccines, this approach has the potential for rapid vaccine production that can aid worldwide distribution.
- Protein-based: This is a previously proven strategy. It does not use the live virus, making it safer to produce.
- Recombinant Nanoparticle: This is a strategy similar to the protein-based strategy that produces a good immune response.
- Viral Vector: This approach makes rapid vaccine production possible. This approach may offer an additional advantage of inducing an immune response to both the virus that causes COVID-19 as well as the vector virus.
Unlike their treatment counterparts, vaccine development for COVID-19 is a lengthier process. Current timelines suggest it will take anywhere from 12-18 months before we see the first licensed vaccine. Unfortunately, no current vaccines against COVID-19 exist and we cannot simply repurpose one—at least not at this time.
Currently, vaccine candidates must undergo many steps before they can become licensed. Candidates can fail at any point in the process. This is a common risk with any drug development program. However, when dealing with an emerging infectious disease candidate, you also run the risk of the disease dissipating before reaching pivotal trials. This was seen with both SARS and Zika, which lost important government funding before development was completed.
Effective treatments will reduce morbidity, mortality, and infectivity from COVID-19, thereby reducing the rates of hospitalization and helping free-up currently overwhelmed healthcare systems. This would result in better quality of care and reduced death rates due to COVID-19. Treatments that rapidly clear the virus from the body also have the potential to reduce the period that a patient can infect others, contributing to infection control. In the best-case scenario, COVID-19 drugs could be used as prophylaxis in individuals close to or caring for infected patients until an approved vaccine becomes available.
Currently, there are no drugs or therapeutics approved by the US Food and Drug Administration (FDA) to prevent or treat COVID-19. However, researchers are actively investigating therapeutics that could potentially be effective in combatting the disease, including some already existing antiviral drugs. Some different strategies currently under investigation include:
Chloroquine is a widely used drug routinely prescribed for the treatment of malaria and certain inflammatory conditions. Found to be a potential, broad-spectrum antiviral in 2006, chloroquine and its derivative hydroxychloroquine are currently under investigation for pre-exposure and post-exposure prophylaxis of SARS-CoV-2 infections and treatment of patients with COVID-19. Recently, the FDA issued an emergency use authorization, allowing for the use of chloroquine and hydroxychloroquine in hospitalized adults and adolescents with COVID-19 for whom a clinical trial is not available or participation is not feasible.
Developed by Gilead originally as a treatment against malaria, Remdesivir is also among the COVID-19 treatment candidates being studied. Remdesivir is an intravenous drug with broad antiviral activity that inhibits viral replication. It has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related beta coronaviruses. After a recent case report showed that treatment with remdesivir improved the clinical condition of the first patient infected by SARS-CoV-2 in the United States, a phase III clinical trial was launched in Wuhan in February 2020.
Researchers are also investigating the use of T-cell therapies against the novel coronavirus. CAR T Cell therapy targets IL-6 production, which can potentially shut down cytokine storms and stop disease progression into the lower lung.
Another strategy under investigation is inactivated convalescent plasma. This consists of injecting active COVID-19 infected patients with plasma from previously infected patients who have recovered. This approach has several drawbacks ranging from not fully understanding the body’s ability to generate a protective response to the ability to collect enough antibody-rich plasma from the previously infected.
So, what’s next?
The good news is that the vaccine community is seeing more collaboration than ever before. Major manufacturers are partnering to seek quality COVID-19 vaccine candidates while health authorities, sponsors, CROs, and investigator sites are working together to create streamlined studies that can be stood up and finished at speeds previously not thought possible. Virtual trials and adaptive trial design can help combat the unique challenges present in the age of social distancing, while global medical informatics data can track the disease and help identify quality sites now and in the future. PRA’s Center for Vaccine Research is leveraging this modern approach to trial design and conduct to rapidly adapt to the demands of clinical development during a pandemic.
Research and medical communities are working hard to find a pathway forward with regards to COVID-19. How quickly this disease is brought under control depends as much on individual efforts, such as social distancing and handwashing, as it does on treatments and vaccines. What cannot be lost in this global effort are the communities who are not in as good of a position to deal with this threat.
It is likely that these treatments and vaccines, once developed, will go to high-income countries first—even if COVID-19 has since moved on. This will leave low-income and underserved countries to continue to face the pandemic with little to no resources. Knowing this, what can be done to ensure equal distribution? Should treatments and vaccines be reserved for those countries still struggling to control the disease? And who will finance the developmental and production costs if these countries are unable to pay for these new therapies or vaccines?
Safe, effective treatments and vaccines are critical in controlling COVID-19—but equitable distribution of these life-saving measures is equally important. As drug development continues for COVID-19, we must also seek answers to these questions.
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