E.Since the SARS-CoV-2 virus was first identified and sequenced by researchers in China a year ago, a tidal wave of research into the pathogen and the associated disease COVID-19 has flooded the scientific literature. An analysis published as preprint last month found that more than 84,000 articles on COVID-19 were published in the first eleven months of 2020.
Even with this production and the recent introduction of vaccines against the disease, researchers studying the virus are unwilling to put it on hold and turn to other problems. Here are some of the key areas where we are likely to see progress in understanding this year.
Finding out the origin of SARS-CoV-2 is important, according to the EcoHealth Alliance’s disease ecologist Jonathan Epstein, as knowing how the virus got into humans can provide clues on how to prevent future overflows. The SARS outbreaks of 2003 and 2004 spurred research (which Epstein was a part of) that identified horseshoe bats as a reservoir for this family of coronaviruses, he notes, but it’s still not known exactly how either virus got it from bats to humans. Understanding whether SARS-CoV-2 jumped straight from bats into humans, or whether it infected a wild or domesticated intermediate species first, would help pinpoint certain human activities that could put us at risk for future zoonotic events, he says .
The World Health Organization (WHO) has convened a team to investigate the origins of the virus that traveled to China earlier this month, WHO chief Tedros Adhanom Ghebreyesus said in a January 5 briefing. According to WHO spokesman Tarik Jašarević, the team plans to review hospital records from the end of 2019 to identify diseases that may have been COVID-19, interviewing people who are the first known cases and find out which animals were being traded in a market in Wuhan with some early infections and possibly other local markets at the time of the outbreak and where those animals came from. Jašarević didn’t say when the team’s results might be available.
In addition to prevention, another advantage of knowing the animal origin of coronaviruses is the possibility of developing drugs against them in advance, namely “largely neutralizing antibodies that not only raise SARS-2 but also other related coronaviruses that we know about that they occur in animals can hit reservoirs, ”says virologist Kartik Chandran from Albert Einstein College of Medicine in New York. This is a long-term goal of his current work to identify potent antibodies that can be used as a COVID-19 drug. And he says it will also be important to find out how vaccines can be developed that offer protection against a wide swath of such coronaviruses. “From a research perspective, this will be a major challenge over the next few years.”
Even with effective vaccines, humanity is likely to stick with SARS-CoV-2, much like the cold-causing coronaviruses and influenza, Chandran says. This means that effective treatments for the disease are still needed. A problem with current monoclonal antibody treatments is that large amounts of IV must be administered, which creates logistical challenges. “If we can make these things strong enough, ideally we can give them by intramuscular injection instead of giving them intravenously – that would make a world of difference,” he says. “But that requires a jump in potency, which is pretty significant.”
To date, a stand-alone monoclonal antibody, bamlanivimab, and a combination of two, casirivimab and imdevimab, have received emergency approval from the U.S. Food and Drug Administration (FDA). Both treatments have been tested in clinical trials in people with mild or moderate illness. The studies found that those who received them had about a third of the risk of going to the emergency room or being hospitalized in the next four weeks compared to those who received a placebo. Other treatments currently available include the antiviral remdesivir and the steroid dexamethasone, each used for some hospital patients, as well as convalescent plasma, which, according to a small study published this week, halved the risk of severe respiratory disease within three days of the onset of symptoms.
“We were encouraged to see the rapid pace of development of monoclonal antibodies,” says Esther Krofah, executive director of the FasterCures center at the non-profit Milken Institute. “But I think there is still a lot to do, especially in the outpatient area.” In particular, a small molecule drug that could be taken at home by patients to reduce the likelihood of hospitalization would ease some of the pressure on the healthcare system. One such drug that she is keeping an eye on, camostat mesilate, is a protease inhibitor that is currently being tested in several clinical trials.
FasterCures is tracking more than 300 potential vaccines and treatments for COVID-19 that are in various stages of development. Krofah believes that many current clinical studies will fail to provide conclusive results due to poor design or problems recruiting enough patients. One promising approach, she says, is the so-called master’s protocol studies, which compare different treatments both with each other and with a placebo.
A number of such studies, sponsored by the National Institutes of Health, for example, some of which are expected to be completed later this year, test immunomodulators, monoclonal antibodies, and blood thinners in groups of COVID-19 patients. In other studies, some reused antibiotics and an antifungal drug have shown promise and could make it into the clinic this year, says Yasmeen Long, also from FasterCures.
As SARS-CoV-2 continues to mutate, researchers need to determine whether available vaccines are effective against newer variants, according to Chandran, such as variants B.1.1.7 and 501.V2, which have received a lot of attention in recent weeks. Akiko Iwasaki, an immunologist at Yale University, says current variants “are likely to be covered by existing vaccines, but new variants may emerge in the future that evade the current vaccine” – which means monitoring the virus variants should be a priority to have.
To date, the US has sequenced 58,560 SARS-CoV-2 samples, compared to the 209,038 in the UK. The New York Times Reports, but an official from the Centers for Disease Control and Prevention told CNN that the agency and its partners are working to double the number of viral sequences they publicly release each week to around 6,500.
One of Iwasaki’s current projects is profiling the immune responses of people whose COVID-19 symptoms have persisted for months, a phenomenon known as long-term COVID. “Right now, thousands of people are suffering from long-term COVID,” she says. “But there is very little understanding of how the disease is caused and prolonged for so many people.”
Understanding the mechanism of the disease could point the way to treatments, as well as shed light on other cases of chronic diseases associated with initial viral infection. After recently discovering that COVID-19 patients in the hospital have different antibodies against their own proteins, so-called autoantibodies, she and her colleagues have started to investigate whether such autoantibodies play a role in long-term COVID.