Current treatments for COVID-19: Ongoing challenges and successes
By Edward Chen and Yidan Gao, Edited by Kimmy Ye and LisaMichelle Pecaro
After a short plateau from August to September, a third wave of COVID-19 began in October. Concerningly, this wave has continued into the current month of December and case counts are still at an all-time high; there is no sign that this upsurge is disappearing anytime soon.
However, progress in vaccine development has been strong. 63 vaccines are in clinical trials, of which 18 are in large-scale efficacy tests, and the US Food and Drug Administration (FDA) has already issued its first emergency use authorization (EUA) for a COVID-19 vaccine. This EUA, announced on December 11, allows widespread distribution of the Pfizer-BioNTech COVID-19 vaccine. Already, people have been vaccinated outside of clinical trials, though this is not to say that there are no additional challenges ahead. There are still many issues that must be considered, including the duration of the antibody response, the dosage needed for effective protection, and the distribution of the vaccine throughout the nation.
The Pfizer-BioNTech COVID-19 vaccine is an mRNA vaccine. This type of vaccine contains messenger RNA, or mRNA, that cells can use to make a viral protein. When someone is vaccinated, their cells can produce non-infectious viral protein from the mRNA. This non-infectious viral protein is then presented to immune cells, which allows the immune system to prepare for a potential encounter with the infectious SARS-CoV-2 virus. While mRNA vaccines are new and none have been approved before, they have previously been studied for influenza, Zika virus, rabies, and even cancer. The FDA holds mRNA vaccines to the same, high standards of safety and efficacy as they do for other types of vaccines.
During this critical time, the FDA has issued EUAs for two drugs against COVID-19: remdesivir and bamlanivimab. Though both are used to fight COVID-19, these two medications have different mechanisms of action. Remdesivir is an antiviral agent that targets and interferes with viral replication. Bamlanivimab, on the other hand, is a monoclonal antibody that binds to and stops viruses before they can enter our cells.
Remdesivir, approved on October 22, is a viral RNA polymerase inhibitor originally developed to treat the Ebola virus. SARS-CoV-2 is also an RNA virus, and so it requires an enzyme called RNA-dependent RNA polymerase to replicate itself. Remdesivir impedes this process and halts viral replication. A recently published study in the New England Journal of Medicine showed that remdesivir, in combination with the drug baricitinib (an immunosuppresant thought to reduce damaging immune hyperactivation), reduced the recovery time for COVID-19 patients. Other than its application in ameliorating COVID-19, remdesivir is also effective in treating the Ebola virus, another RNA virus. During the Ebola epidemic in 2018, after its effectiveness was demonstrated in rhesus monkeys, remdesivir was tested in the Democratic Republic of the Congo.
Although the FDA approval is promising, there are strict guidelines around treatment with remdesivir. First, the drug must be injected directly into blood vessels (i.e., administered intravenously). Second, remdesivir is only approved for hospitalized patients who are 12 or older and who weigh at least 40 kilograms (around 88 pounds). Finally, remdesivir has rare, but potentially severe side effects, such as liver damage, which is indicated by elevated transaminase levels. Therefore, remdesivir treatment requires close monitoring of liver function.
Upon FDA approval, controversies arose as to the efficacy of remdesivir. In a World Health Organization clinical trial with 12,000 COVID-19 patients, remdesivir treatment did not reduce mortality. At the end of the day, this dispute remains a hot debate, which may be why remdesivir has an EUA but not a full FDA approval.
In addition to remdesivir, another medical intervention, bamlanivimab, was issued an EUA by the FDA. Bamlanivimab is developed by Eli Lilly and Company and is meant to treat mild to moderate COVID-19. Bamlanivimab is an IgG1 antibody that can bind to the receptor binding domain of the SARS-CoV-2 spike protein. This interaction neutralizes the virus by preventing it from binding to the ACE2 receptor. This stops the virus from subsequently entering into host cells. In this case, the drug directly protects patients by preventing viral entry into cells. Typically, our immune system generates antibodies to defend us; however, this process takes time—time that we cannot afford in our fight against COVID.
Usage guidance for bamlanivimab is similar to remdesivir. Bamlanivimab also requires intravenous infusion and the age and weight requirements are the same. Unlike remdesivir, however, bamlanivimab is approved for non-hospitalized patients as well. This month, the US purchased an additional 650,000 doses of bamlanivimab. The federal government had previously purchased 300,000 doses of bamlanivimab.
Finally, corticosteroids have also been used as part of COVID-19 treatments. The rationale is that corticosteroids have benefited patients with other pulmonary infections, such as acute respiratory distress syndrome resulting from asthma, severe influenza viral infection, and severe acute respiratory syndrome (SARS), a disease caused by SARS-CoV-1 and commonly known as SARS. Corticosteroids are potent immunosuppressants and may therefore benefit patients who suffer from an overactive immune system, as seen in severe COVID-19 cases. In the quest to find a treatment for COVID-19, scientists launched a national clinical trial called the RECOVERY trial “to identify treatments that may be beneficial for people hospitalised with suspected or confirmed COVID-19.” In this trial, scientists found that dexamethasone, a corticosteroid, decreased inflammation-mediated lung injury. This trial has also investigated other drugs, from antibiotics and anti-inflammatories to antibodies and aspirin.
Unfortunately, corticosteroids do have side effects as well, including osteonecrosis of the femoral head, which has been was reported in patients who recovered from severe SARS after corticosteroid treatment. This unusual disorder is caused by a reduced blood supply to the hip joint, resulting in the death of bone cells. The underlying pathogenesis is likely due to oxidative stress and disorders of the vascular endothelium. This condition significantly impairs the well-being and functioning of patients, and decreases quality of life as well as increases public health burden due to the need for long-term supportive care.
Scientists are working hard to combat this public health crisis. On April 20, 2020, the FDA announced the specialized Coronavirus Treatment Acceleration Program (CTAP) to focus on COVID-19 interventions. The FDA continues to rapidly update the progress of clinical trials for medications and vaccines. In fact, on December 17, an FDA advisory panel recommended granting an EUA for Moderna’s mRNA-1273 vaccine. An official FDA authorization is expected to come later today, December 18.
At the same time, even though researchers are in the lab around the clock, it is our responsibility to acknowledge our collective social responsibilities, including wearing a mask and maintaining social distancing. We will eliminate the virus faster by working together with scientists and following scientific recommendations.
Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on December 18, 2021.
Edward Chen is a master's student studying immunology. He's also the national president of Students vs. Pandemics. @EdwrdChen