Current treatments for COVID-19: Exploring the challenges and successes

By Yidan Gao, Edited by Edward Chen

After a short plateau from August to September, a second wave of COVID-19 began in October and has continued into the current month of December. Case counts are still at an all-time high and there is no sign 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 FDA has already issued its first emergency use authorization for a COVID vaccine. This emergency use authorization, announced on December 11, allows widespread distribution of the Pfizer-BioNTech COVID-19 vaccine. People have already been vaccinated outside of clinical trials. This is not to say that no challenges lay ahead. There are still many issues that must be considered including the duration of the antibody response, the dosage needed for protection, and the distribution of the vaccine around 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 the immune system, 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 previously been approved, they have previously been studied for influenza, Zika virus, rabies, and even cancer. The US Food and Drug Administration (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 recently issued emergency use authorization for two drugs against COVID-19: remdesivir, sold under the brand name Veklury, and bamlanivimab. These two medications have completely different mechanisms. Remdesivir is an antiviral medication that targets viral replication. Bamlanivimab, on the other hand, is a monoclonal antibody that stops viruses before they enter our cells.

Remdesivir, approved on October 22, is a viral RNA polymerase inhibitor originally developed to treat the Ebola virus. The coronavirus is an RNA virus and 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 remdesivir, in combination with the drug baricitinib, reduced the recovery time of COVID patients. Other than its application in ameliorating COVID-19, remdesivir is also effective in treating the Ebola virus, another RNA virus. After its effectiveness was demonstrated in rhesus monkeys, remdesivir received emergency approval in 2018 during the Ebola epidemic in Congo.

Although the FDA approval is promising, there are strict guidelines around remdesivir treatment. First, the drug must be administered intravenously. In addition, remdesivir is only approved for hospitalized patients 12 or older that weigh at least 88 pounds. Dosage recommendations are available on the FDA’s website, and treatment lasts 5-10 days. A severe , but very rare, side effect of remdesivir is 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 patients, remdesivir treatment did not reduce mortality. Several organizations, including the NIH, have also raised concerns about the scientific data behind remdesivir’s FDA approval, which might have involved political pressure. At the end of the day, this dispute remains a hot debate.

In addition to remdesivir, another medical intervention, bamlanivimab, was recently approved by the FDA. Bamlanivimab is developed by Eli Lilly and an emergency use authorization for its use in treating mild to moderate COVID-19 was approved on November 9. Bamlanivimab is a neutralizing IgG1 antibody that can bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. This interaction neutralizes the virus by preventing its binding to the ACE2 receptor and subsequent entry into host cells. In this case, the drug directly protects patients by preventing virus 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. This readily available commercial antibody significantly benefits individuals.

Administration guidance for bamlanivimab is similar to remdesivir. Bamlanivimab also requires intravenous infusion and the age and weight requirement remains. Unlike remdesivir, however, bamlanivimab is approved for non-hospitalized patients. This month, the US government purchased an additional 650,000 doses of bamlanivimab. The US had previously purchased 300,000 doses of bamlanivimab.

Corticosteroids have also been used as part of COVID 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, a disease caused by a 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 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 decreased inflammation-mediated lung injury. This trial has also investigated other drugs from antibiotics and anti-inflammatory drugs to antibodies and aspirin.

Unfortunately, corticosteroids do have side effects as well, including osteonecrosis of the femoral head. This 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 also causes an additional public health burden due to the need for long term supportive care.

Scientists are working very 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. As a matter of fact, on December 17th, the FDA advisory panel gave its endorsement for Emergency use authorization for Moderna’s mRNA-1273 vaccine. The official FDA authorization is expected to come today, December 18th. At the same time, 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 January 3, 2021.

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