The science of COVID-19 is evolving as fast as the novel coronavirus spreads, with researchers trying to end the pandemic with new tests, treatments, and potential vaccines. Because SARS-CoV-2 had never been seen before it emerged in Wuhan, China, last year, scientists are starting from scratch, hoping to contain and neuter the virus as it continues its devastating march across the globe.
Here’s a look at where the major developments in testing, treatments, and vaccines stand:
TESTING
Most Americans who’ve been lucky enough to get a coronavirus test when they needed one have received a reverse transcription polymerase chain reaction or RT-PCR test, but testing capacity is strained as labs run short of crucial reagents and capacity. Here are a few of the new testing technologies that scientists and public health experts hope can help us manage the virus as states contemplate an end to quarantines.
Abbott Labs ID Now Test
The Illinois-based company Abbott Labs announced in March that it had received FDA emergency use authorization for a coronavirus test that takes as little as five minutes to confirm a positive diagnosis for the virus and 13 minutes to clear a sample as negative. The tests are similar to the normal polymerase chain reaction tests but run on the company’s mobile ID NOW platform rather than needing a lab to process results, which can sometimes take days to get. When it announced the FDA’s emergency use authorization, Abbott Labs said it expected to soon be able to produce 5 million tests a month and public health experts called it a “game changer.” So far, however, states have only received a few thousand of the tests. Pharmacy chains such as CVS and Walgreens have announced small pilot programs for drive-through testing that would rely on the ID NOW testing platform. The Philadelphia Department of Public Health is expected to deploy the devices in late May or early June.
Cepheid
Before Abbott’s rapid test, Cepheid was among the first companies to receive an FDA emergency use authorization for a rapid coronavirus test. Swabs are placed in a cartridge pre-packaged with the reagents necessary to conduct the test and run on the company’s Xpress point-of-care system. The Cepheid test takes 45 minutes to complete.
Experts warned that the test has flaws. The Cepheid test “performed equivalent to the other platforms with patients that had high and moderate loads of virus,” said Alan Wells, a pathologist at the University of Pittsburgh Medical Center. “However, with lower loads of virus, a large fraction of these patients were not detected as positive.”
Pixel by LabCorp
In mid-April, LabCorp won FDA approval for a $119 test kit that will allow people to swab their own nose at home and then ship the specimen to the company for processing. It’s initially being rolled out to health-care workers and first responders but will become more widely available, the company said. Consumers who want to buy it will complete an online eligibility survey and then a doctor decides whether to authorize the test.
Antibody tests
Public health experts view antibody testing as a critical tool for states to begin loosening up quarantine rules and help restart the economy. Unlike the polymerase chain reaction (PCR) tests, which look for the coronavirus’s genetic material in a patient’s bloodstream, antibody tests look for the body’s response to the virus in the form of antibody production. Antibody tests aren’t as useful in diagnosis as PCR tests, since they only produce a positive result once the body has begun to fight off the infection. However, the rapid tests—often taking just minutes—can tell you if someone has been exposed to SARS-CoV-2 and developed signs of possible immunity. That information, experts believe, could be helpful in determining who faces less risk in returning back to the workplace and how far the virus has spread within a given population.
The FDA granted the first emergency use authorization for an antibody test to North Carolina-based company Cellex. Since then, Chembio Diagnostic Systems, Ortho Clinical Diagnostics, and Mount Sinai Laboratory have all received FDA emergency use authorizations for antibody tests, with more tests awaiting approval. Meanwhile, at least 90 antibody tests have reached the U.S. market—many from China—without undergoing that more rigorous FDA review process, creating concerns about quality and accuracy.
But scientists still aren’t sure that antibodies have any bearing on the progress of COVID-19 cases. “I still have not seen convincing evidence that naturally induced antibodies alter the course of disease,” David Ostrov, a virologist at the University of Florida, told The Daily Beast. If antibodies don’t actually defeat the novel-coronavirus, then the presence of antibodies would only indicate a person got infected. It wouldn’t indicate that the person is immune.
In early May, Blood Connection—a South Carolina blood bank with multiple locations—began offering free SARS-CoV-2 antibody tests to all donors. Blood Connection announced it is working with area hospitals to establish a supply of convalescent plasma.
Sewage surveillance
Since scientists learned that the coronavirus shows up in feces, researchers have been looking into testing sewage in order to find infections in municipal-sized populations. Researchers have long used sewage surveillance as a method to spot early signs of diseases like polio—but it could be particularly important for COVID-19, given that asymptomatic and presymptomatic patients may be responsible for a number of transmissions. A team in the Netherlands published a study showing they had found evidence of the virus in sewage weeks before the country had a first confirmed test in a patient. Researchers at MIT also published a study that claimed sewage samples from Massachusetts, taken in March, suggest a higher rate of COVID-19 infection than the state’s official tally of confirmed positive cases.
However, the National Institutes of Health downplayed the danger. “Importantly, detection of SARS-CoV-2 RNA in wastewater does not imply that the virus is viable and able to infect humans,” the NIH announced. “Coronavirus in wastewater is relatively short-lived.”
TREATMENTS
Remdesivir
The antiviral compound, originally researched as a potential therapy for Ebola, is now in phase-three clinical trials to test its efficacy in COVID-19 patients. Scientists hope that the drug can interfere with the coronavirus’s ability to reproduce within cells. A recent study of 53 severely ill patients with COVID-19 showed that over two-thirds improved after receiving the drug, including 17 patients who no longer required a ventilator after 18 days. The lack of a control group for the study, however, makes the results hard to compare against results from standard care.
The FDA quickly approved remdesivir for emergency use, but the Trump administration has maintained control over the drug’s distribution. Gilead, the California pharma that makes remdesivir, initially donated 607,000 doses of the drug to the federal government. In mid-May, Gilead reportedly donated another 333,000 doses. Those 940,000 doses are enough to treat around 100,000 patients.
Gilead, the California pharma that makes remdesivir, received tens of millions of dollars in government support as it developed the drug. But government agencies never asserted any patent rights to remdesivir, meaning they have no power to control Gilead’s pricing and distribution of the drug.
The FDA quickly approved remdesivir for emergency use, but the Trump administration has maintained control over the drug’s distribution. Gilead initially donated 607,000 doses of the drug to the federal government. In mid-May, Gilead reportedly donated another 333,000 doses. Those 940,000 doses are enough to treat around 100,000 patients.
Doctors in several hospitals—including some struggling with a surge of COVID-19 cases—complained they could not get their hands on remdesivir. Massachusetts General Hospital told The Washington Post it’s in line to receive remdesivir. But two other hospitals in the Boston area reported they had been denied the drug.
The World Health Organization has included remdesivir as one of four major treatments in its massive “Solidarity” trial, which involves 3,500 patients at 400 hospitals in 35 countries.
On May 27, Swiss pharma Roche announced it’s planning to test a mix of tocilizumab and antiviral drug remdesivir in the treatment of severe cases of COVID-19. The global phase-three trial would involve 450 patients in the United States, Canada and Europe.
Tocilizumab
Tocilizumab is an anti-inflammatory drug used to treat rheumatoid arthritis but researchers have theorized that it might be effective in treating the deadly inflammation at the heart of the “cytokine storm” that plagues many suffering from COVID-19. In some severely ill patients, the body’s immune response to the virus results in an excess of cytokine proteins, which can damage lung tissue—an effect which also made the 1918 flu pandemic so lethal.
Chinese researchers studied tocilizumab with severely ill COVID-19 patients early on in the outbreak and included the drug in their treatment guidelines. In late March, the FDA granted approval to Tocilizumab producer Roche for a Phase III trial of the drug’s efficacy against the coronavirus. Researchers in China, Italy, and Switzerland have also launched their own Phase II studies of the drug.
On May 26, Hackensack Meridian Health in New Jersey announced early results from a tocilizumab trial involving 3,000 hospitalized COVID-19 patients at 13 hospitals. Tocilizumab “appears to improve survival among critically-ill intensive care unit patients,” trade magazine NJBIZ explained.
Other anti-inflammatory drugs, like Eli Lily’s Baricitinib and Regeneron’s Kevzara, are under study to see if they could have a similar effect in taming the body’s immune response to the disease.
On May 27, Swiss pharma Roche announced it’s planning to test a mix of tocilizumab and antiviral drug remdesivir in the treatment of severe cases of COVID-19. The global phase-three trial would involve 450 patients in the United States, Canada and Europe.
REGN-COV2
New York pharma Regeneron has created a new “antibody-cocktail” for treating COVID-19. To develop REGN-COV2, Regeneron re-used technology it invented for an earlier Ebola treatment. Trials could begin in June. And if REGN-COV2 shows promise, Regeneron plans to devote an entire factory to producing the cocktail, with the goal of making “a couple hundred thousand” doses available to hospitals by the end of the summer.
Sarilumab
Sarilumab is another anti-inflammatory drug that, like tocilizumab, could help to calm the cytokine-storm immunity-response that can lead to organ failure and appears to be a major cause of death in COVID-19 cases. Pharmaceutical firms Sanofi and Regeneron undertook a major trial of sarilumab starting in mid-March, but by late April had significantly scaled back its testing. The companies reported “no notable benefit” after testers administered Kevzara, a brand of sarilumab, to patients with “severe” cases of COVID-19. “Emerging evidence with Kevzara and other repurposed drugs in the COVID-19 crisis highlight the challenges of making decisions about existing medicines for new viral threats using small, uncontrolled studies,” Regeneron president George Yancopoulos said.
Anakinra and Siltuximab
Anti-inflammatory drugs tocilizumab, sarilumab and siltuximab work by blocking the body’s IL-6 receptor, which helps to regulate immune-response. But the IL-1 receptor might also play a role in the cytokine-storm effect that results from an overactive immune system destroying a patient’s organs while also trying to eliminate the SARS-CoV-2 virus. Blocking IL-1 in COVID-19 patients could have the same benefits as blocking IL-6.
In early April, doctors at University Hospital, Ghent in Belgium began testing the anti-inflammatory drug anakinra, which blocks Il-1, in conjunction with the IL-6-blocker siltuximab. Anakinra is worth looking into, Stephen Jameson, a University of Minnesota pathologist, told The Daily Beast. But siltuximab, tocilizumab and sarilumab seem more likely to work, Jameson added. “IL-6 seems to be especially volatile in patients.”
Convalescent Plasma
A national team of doctors and researchers, led by Dr. Arturo Casadevall from John Hopkins Bloomberg School of Public Health, received FDA approval to study the effect of convalescent plasma in treating the infected. The study is looking at whether the antibodies developed in the blood serum of recovered patients will go to work against the disease when transfused into sick patients. Since the trial first began, hospitals and universities in Connecticut, Florida, New Jersey, Louisiana, Ohio, Texas, and Wisconsin, among other locations, have begun administering convalescent plasma to those sickened with COVID-19.
The Mayo Clinic in Minnesota, working with the FDA and the federal Biomedical Advanced Research and Development Authority, has developed rigorous standards for drawing and administering plasma. More than 2,100 hospitals and clinics have signed up for Mayo’s COVID-19 Expanded Access Program. Nearly 4,800 physicians treating more than 10,000 patients are involved.
As of May 5, around 6,000 patients have received infusions. There’s no published, peer-reviewed analysis yet on how all of those patients responded. The scientific community is still waiting on data from larger randomized control trials underway to check the effectiveness of the treatment but two smaller uncontrolled studies from China showed symptom improvement and that patients were able to wean themselves off ventilators after receiving antibody-rich plasma.
A study by researchers at the University College London, published in mid-May, found that patients who’ve been infected with human-coronaviruses other than the novel-coronavirus demonstrated a degree of immunity against the latter, more-lethal virus. Moreover, these patients’ plasma “exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes,” perhaps indicating that a wide range of coronavirus antibodies could work against the novel-coronavirus.
Chloroquine/hydroxychloroquine
Early research into the anti-malarial chloroquine (and the closely related hydroxychloroquine) during the 2003 SARS epidemic led many researchers to believe the cheap and widely available drug could make cells inhospitable to the virus by altering the pH balance in the parts of the cell where the invading pathogens attach. Early lab research in China suggested that the drug might be effective in clinical trials, and that was echoed by a dubious study published in France. Celebrity endorsements of the drug from the likes of Elon Musk and President Trump have turned the research into chloroquine’s effectiveness from a scientific debate over evidence into a partisan battle.
Thanks in part to Musk and Trump’s endorsements, sales of chloroquine doubled between March and April. In March alone, pharmacists fulfilled 830,000 prescriptions for a generic version of the drug, up from 460,000 prescriptions in March 2019.
In the meantime, legitimate research into whether or not the drug lives up to the hopes has continued. The World Health Organization and a number of universities and labs around the world have launched a series of clinical trials looking at chloroquine’s effectiveness.
One observational study carried out by the Department of Veterans Affairs found no benefit to chloroquine. But that didn’t stop the department from treating 1,300 coronavirus patients with the drug.
A number of researchers and hospitals have stopped using chloroquine because of potentially severe side effects. A Brazilian study gave high and low doses of chloroquine to 81 COVID-19 patients, but halted the trial after patients receiving the higher doses experienced more deaths and some developed cardiac arrhythmias.
Doctors in Nice, France halted a hydroxychloroquine trial after patients developed potentially dangerous arrhythmias and hospitals in Sweden have similarly stopped prescribing chloroquine after patients experienced severe side-effects.
On May 18, Trump said he has been taking hydroxychloroquine for more than a week in the hope of preventing a coronavirus infection, even though the drug isn’t yet a proven treatment -- and despite the well-documented risks.
Four days later on May 22, a study of 96,000 hospitalized coronavirus patients on six continents found that those who received chloroquine had a significantly higher risk of death than with those who did not. On May 25, the World Health Organization announced it was suspending its own hydroxychloroquine trial. The WHO stated it preferred to "err on the side of caution."
“Hydroxychloroquine and chloroquine are increasing issues with arrhythmias and have yet to prove much benefit for treating COVID-19,” Edwin Hayes, an infectious-disease doctor with the Prisma Health Hospital system in Columbia, South Carolina, told The Daily Beast. “Based on the data from studies so far, it appears the risks are outweighing the benefits, and other treatments being investigated are garnering more interest, including convalescent plasma and remdesivir.”
On May 27, National Institute of Allergies and Infectious Diseases director Anthony Fauci told CNN anchor Jim Sciutto that negative data on hydroxychloroquine was “quite evident.” “I'm not so sure that it should be banned, but clearly the scientific data is really quite evident now about the lack of efficacy for it.” The same day, France banned the use of hydroxychloroquine in treating COVID-19.
Lopinavir/ritonavir/ribavirin/beta interferon
Early on in the coronavirus outbreak, the World Health Organization included lopinavir and ritonavir, two antiviral drugs used to treat HIV/AIDS, in their Global Solidarity Trial of promising drugs, in part based on early studies of the antivirals against the SARS outbreak in 2003.
Researchers around the world are investigating the drug combination in a series of clinical trials, but early results have been mixed. One study from researchers in China, the United States and the United Kingdom involving nearly 200 patients found no benefit to the drug combination beyond standard care.
A separate study under Kwok-Yung Yuen at Hong Kong University tested a three-way antiviral treatment involving a ritonavir-lopanivir combination, the antiviral-drug ribavirin plus a multiple-sclerosis drug called beta interferon. "Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild-to-moderate COVID-19," the Kwok-Yung’s team wrote.
The World Health Organization has included lopinavir, ritonavir and beta interferon in its massive “Solidarity” trial, which involves 3,500 patients at 400 hospitals in 35 countries.
Favipiravir
The Russian Direct Investment Fund has teamed up with Russian biotech startup ChemRar to test favipiravir at 18 clinics in Moscow treating novel-coronavirus patients. No fewer than 16 separate studies involving the drug are underway in India, Italy, the United Kingdom and the United States.
Sixty percent of people who received the treatment tested negative for COVID-19 on the fifth day, Russian Direct Investment Fund CEO Kirill Dmitriev claimed. But a trial in Japan showed no clear evidence that favipiravir worked on COVID-19, the Japanese health ministry reported in mid-May.
“It’s a broad antiviral so some effect is likely,” Stephen Jameson, a University of Minnesota immunologist, told The Daily Beast. But Jameson said it’s “unclear” whether favipiravir or any antiviral drug will cure COVID-19. “As long as benefits outweigh side effects, all are worth exploring,” he added. “Unlike snorting bleach.”
Stem cells
The FDA has approved a Texas company, Hope Biosciences, for a trial on stem cell therapy. The theory is that the stem cells could reduce inflammation and strengthen the immune system of some patients. “Let’s give it to these people who are at high risk,” CEO Donna Chang told the Houston Chronicle. “Then also, how about our frontline first responders, how do we protect those folks? We can take a certified donor and make large quantities of stem cells.”
In early May, Australian biotech firm Mesoblast announced it’s begun a randomized, controlled study of its own stem-cell therapy remestemcel-L in the treatment of COVID-19.
Proning
Some critical care experts have suggested a simple change in body position could improve outcomes in some COVID-19 patients. Lying on the back, as most people do in hospital beds, impedes lung function. The Intensive Care Society, a professional organization in the U.K., is recommending that patients receive oxygen support in the prone position—belly-down—as long as they are conscious.
Ultrasound
Three pediatricians at the Catholic University of the Sacred Heart in Rome recommended changes in the way doctors assess suspected COVID-19 patients during initial examinations. In order to protect doctors and hospital staff from infection, Danilo Buonsenso, Davide Pata and Antonio Chiaretti advised doctors to forgo stethoscopes and radiological devices and instead assess a patient’s lungs using only a small ultrasound device.
“We believe that such a procedure could reduce health-care workers' risk of exposure and also patient movement from the consultation room to the radiology room,” the pediatricians wrote. “Considering the contagiousness of the virus and the need to reduce nosocomial outbreaks, we strongly suggest promotion of lung ultrasound in this setting.”
Monoclonal antibodies
Numerous companies are trying to figure out which antibodies would be best at recognizing and blocking the new coronavirus so they can make synthetic copies that could, theoretically, be infused into patients. Others are launching trials to determine if existing monoclonals used to treat other diseases like rheumatoid arthritis would be effective in COVID-19 cases.
University of Washington scientist Alicia Bui looks for antibodies in convalescent plasma.
Karen Ducey/GettyVitamin D
Researchers at Northwestern University analyzed patient data from 10 countries and found a correlation between low vitamin-D levels and hyperactive immune systems. Multiple studies have identified the so-called “cytokine storm” that results from an excessive immune response as a major source of mortality in COVID-19 patients. Vitamin D, the Northwestern University researchers noted, strengthens immunity and could help to prevent cytokine storms.
Ultraviolet light
It’s well-known that ultraviolet light kills pathogens. But despite Pres. Donald Trump’s claim to the contrary, it’s not safe to shine U.V. light directly onto, or into, living human beings. “U.V. light damages human skin, so it should only be used on objects or surfaces,” the National Academies warned.
Scientists have proposed installing U.V. lights high on the ceilings of buildings and using fans to draw air up toward the lights. Such installations could be safe and might help sterilize indoor air, but they might also be prohibitively expensive for widespread use.
VACCINES
Moderna
Human clinical trials for Moderna’s mRNA-1273 vaccine got underway in mid-March at Seattle’s Kaiser Permanente Washington Health Research Institute. National Institute of Allergies and Infectious Diseases director Anthony Fauci labeled the Moderna trials an “important first step” in battling the global pandemic.
The first patients enrolled in phase-one trials received doses starting on March 16. Moderna dosed three groups of 15 patients each, all between the ages of 18 and 55, with 25 micrograms, 100 micrograms and 250 micrograms of mRNA-1273, respectively. The 25- and 100-microgram groups received two doses of the vaccine within 43 days. The 250-microgram group got just one dose.
Two months later, Moderna announced the tentative good news. “Dose-dependent increases in immunogenicity were seen across the three dose levels,” the company stated in a release.
The vaccine also appears to be safe, Moderna added. “MRNA-1273 was generally safe and well tolerated, with a safety profile consistent with that seen in prior Moderna infectious disease vaccine clinical studies.”
“More data is needed,” Fei Wen, a University of Michigan immunologist, told The Daily Beast in regard to the early Moderna results. “Regardless, it was a great step forward if we all could look past the political discussions around it.”
Johnson & Johnson
In March, pharmaceutical giant Johnson & Johnson announced that it had selected a lead vaccine candidate and two backups and was expanding its manufacturing capacity to meet production target of over one billion doses. The company said it expected to begin human clinical trials of the vaccine in September, with production beginning in early 2021 if studies showed the vaccine was effective.
PittCoVacc
The University of Pittsburgh Medical Center developed a vaccine candidate for the coronavirus that builds on its previous work on potential vaccines for the Middle East Respiratory Syndrome (MERS). The vaccine, dubbed PittCoVacc, uses a synthetically created portion of the coronavirus’s spike protein to generate an immune response in the skin. It’s delivered by a crystalline microneedle array that’s placed on the skin like a band-aid and feels like velcro. PittCoVacc showed promising results in animal trials and the university is currently working with the FDA to get approval for human clinical trials.
Sanofi
French pharmaceutical company Sanofi has teamed up with GlaxoSmithKline to develop a vaccine based on a synthetically created coronavirus spike protein antigen. The companies say they expect their vaccine will go into human clinical trials in early 2020 and won’t be ready until the second half of 2021.
Sanofi chairman Serge Weinberg told France 2 television that the company’s vaccine will be available in all countries at the same time, if and when the vaccine passes trials. “There will be no particular advance given to any country,” Weinberg said.
Oxford
Oxford University has already begun the clinical trial of its vaccine candidate, ChAdOx1 nCoV-19. The ChAdOx1 vaccine candidate uses an innovative approach known as a viral vector. Researchers used a harmless adenovirus and genetically engineered it to produce the coronavirus spike protein.
Oxford began recruiting volunteers for its study in March and is ramping up production in the event its candidate proves effective. A team led by Sarah Gilbert, a professor of vaccinology, recruited 500 volunteers in several countries for the initial phase of the trial.
Gilbert stressed the difficulty of the testing. “It’s going to be complicated trying to determine vaccine efficacy when the virus transmission in different places is going up and then going down again,” she told Bloomberg. “The trial has to be set up in the right place at the right time and that’s very hard to predict.”
Assuming ChAdOx1 works, production could ramp up quickly. “We would hope to have at least some doses that are ready to be used by September,” Gilbert said in mid-April. “There won’t be enough for everywhere by then, but the more manufacturing we can do starting from now, then the more doses there will be.”
Early results from animal trials were mixed. ChAdOx1 didn’t prevent rhesus macaque monkeys from catching COVID-19 from each other, although the vaccine did appear to lessen the severity of their disease. “It is crystal clear that the vaccine did not provide sterilising immunity to the virus challenge, the gold standard for any vaccine,” William Haseltine, a former Harvard Medical School professor who helped develop early HIV treatments, told The Telegraph. “It may provide partial protection,” Haseltine added.
But even those mixed results could justify further trials of the Oxford vaccine. “We need to remain aware that we’re dealing with biology, which is inherently unpredictable,” Keith Jerome, director of the University of Washington Virology Lab, told The Daily Beast.
Several Others
According to the World Health Organization, there are at least 71 vaccine candidates currently in the works as universities and pharmaceutical companies around the world race to find the only thing that experts say can bring an end to the pandemic. Five additional vaccine candidates are undergoing more intensive clinical evaluation.
MMR vaccine
Two studies have found some correlation between patients who have been vaccinated for measles, mumps and rubella and positive outcomes for COVID-19. The researchers stressed that correlation is not the same as causation, but noted that the measles vaccine “has previously been considered in studies as a base for other coronavirus vaccines.”
Higher rates of vaccination for measles, mumps and rubella among younger people, compared to people over the age of 50, could help to explain why older patients are more vulnerable to the novel-coronavirus, researchers proposed.
