Author: Yuezhe Li
SARS-COV-2 is a coronavirus, named so because its glycoprotein envelope resembles crowns. Like other coronaviruses, SARS-COV-2 is an RNA virus, its genetic material is not preserved in DNA molecules, like humans, but in RNA molecules. Once a virus enters a host cell, the virus will hijack host cell machinery to transcribe and translate its RNA to produce more viral particles.
In total, there are seven identified human coronaviruses. One of these viruses causes severe acute respiratory syndrome, more commonly known as SARS. The symptoms of SARS are influenza-like: fever, malaise, pain in muscles, headache, diarrhea, and shivering. The first SARS outbreak was in southern China in 2002. This SARS epidemic swept 26 countries, caused more than 8000 cases and 774 deaths. Middle East respiratory syndrome, known as MERs, is another disease caused by a coronavirus. Although it is not clear where the virus originated from, camels likely played an important role in passing the virus to humans. Since 2012, 2494 cases of MERS have been reported in 27 countries, with 858 patients reported dead.
Like COVID-19, the viruses that cause SARS and MERS can be transmitted between humans. Unlike COVID-19, they caused fewer cases and deaths, and SARS is only transmitted by patients showing symptoms. STAT news predicts the total US death toll will be between 60,000 and 240,000.
To put the Covid-19 death toll into perspective, Covid-19 deaths could rank similarly to cancer and heart disease (see table). What makes it scary is that COVID-19, unlike the other leading causes of death, is highly contagious.
COVID-19: Current treatment
There is no gold-standard treatment for COVID-19. But some treatments have been applied clinically — they are divided into three categories: antivirals, anti-inflammatories, and antibody-based therapy.
Many antiviral drugs hinder viral replication. For example, Lopinavir/ Ritonavir, a drug combination used to treat HIV infection, limits viral replication by inhibiting a protease that is essential for the virus to mature. Unfortunately, an investigation has shown that Lopinavir/ Ritonavir cannot treat COVID-19 effectively. Another antiviral drug, Remdesivir, developed by Gilead to fight Ebola, has been used to treat COVID-19 patients on a compassionate basis, meaning that some severe COVID-19 patients were treated with Remdesivir even though the drug has not received FDA approval. A recent retrospective study analyzed data from these patients, 40 of the 53 patients, 63%, receiving the proper dose of Remdesivir showed improvements. More recently, a leaked video of Phase 3 clinical trials suggests Remdesivir treatment is effective for Covid-19 patients, even though clinical trial data from China remains inconclusive thus far. More recently, a trial carried out by National Institute of Allergy and Infectious Disease seems to cast a positive light on Remdesivir Covid treatment. This trial is so far the most rigorously designed. However, we are still waiting for the data to be released.
Anti-inflammatory treatments focus on alleviating lungs from an overwhelmed immune system. When human bodies are exposed to pathogens, immune cells secrete cytokines, small signaling proteins, into the bloodstream to recruit additional components of the immune system to fight off infections. However, an overwhelmed immune system produces an excessive amount of cytokines, resulting in lung inflammation and fluid buildup. The excess of fluid causes respiratory distress, which may lead to bacterial pneumonia and an increased risk of mortality.
To reduce risk, doctors are focusing on developing methods to decrease cytokine concentrations. One way is to purify the blood. The FDA has granted an emergency authorization for a blood purification device that removes cytokines from the bloodstream. Another way is to target cytokines with antibodies to inactivate them. Some anti-cytokine drugs, such as Actemra, were initially designed to treat cytokine release syndrome and rheumatoid arthritis. Regeneron, Sanofi, and Roche are currently developing drugs in this category to treat COVID-19.
The antibody-based treatment focuses on using antibodies, either from laboratories or from recovered COVID-19 patients, to neutralize coronavirus. One study showed promise in using plasma from recovered patients to treat severely ill patients. Takeda and Regeneron are developing antibody-based therapy for COVID-19.
Developing vaccines against SARS-COV-2
A vaccine is a biological preparation that provides active acquired immunity to a specific infectious disease. Historically, scientists have used live-attenuated or inactivated viruses to make vaccines. Polio vaccines were generated using inactivated poliovirus. Newer methods, including RNA vaccines and using parts of viral particles or proteins as antigens, are implemented to develop vaccines.
So far, there are 115 vaccines in the R&D landscape for Covid-19. Some big pharma companies, such as Sanofi, GSK, J&J, have joined the race. Big pharmaceuticals developing vaccines is considered necessary by many, as these big firms are more likely to have the ability to mass-produce once they find an effective vaccine. Yet, two smaller companies, Moderna Therapeutics and CanSino Biologicals are quite successful in their vaccine development thus far.
Moderna develops RNA vaccines. Their RNA vaccines contain RNA molecules that encode SARS-COV-2’s spike proteins. These spike proteins are essential for the coronavirus to invade human cells. The RNA molecules are encapsulated in lipid nanoparticles. The vaccine is currently in Phase I clinical trial to test its safety. The results of this clinical trial are anticipated by the summer of 2021.
In contrast, CanSino chose to use adenovirus type 5 vector to deliver DNA that encodes spike proteins into cells. An adenovirus type 5 vector is derived from adenovirus, a DNA virus that causes minimal symptoms and does not incorporate their genomes into host cells. Some adenovirus type 5 vectors are excellent vaccine carriers because they are modified to improve immune response. CanSino has previously used similar techniques to develop Ebola vaccines. Currently, their COVID-19 vaccine is in Phase II clinical trial. Additionally, two other vaccines based on live-attenuated or inactivated viruses are approved for clinical trials in China.
Will vaccines be safe?
Phase I of the clinical trials will test for the safety of the newly developed vaccines. Vaccines might have side effects; for example, flu vaccines may cause fever, headache, nausea, etc. Rarely, vaccines might lead to outbreaks of the disease that it is supposed to prevent. The latest incident happened in 2018 in Pakistan, where polio vaccines triggered poliovirus outbreaks. However, it is irrational to avoid vaccination because of unlikely issues. People choke because of eating food. In 2015, 5051 people died because of choking, but so far, I have yet to see people giving up eating to avoid death by choking.
Pandemics do not happen all the time. But its occurrence causes great pain to society. However, pandemics may also produce positive outcomes. For example, the black death in Europe removed around half of the population, leading to a shortage of labor that resulted in wage increases and granting women more freedom to work outside their households. If countries can use the COVID-19 pandemic to push through necessary reforms (e.g., healthcare in the US and banning wild animal trade in China) and raise awareness of good hygiene, the whole society might gain a long-lasting positive impact.