A proposal to implement universal health care in New York would require a tax increase of “historic proportions” to cover 20 million residents. That’s according to an analysis of the bill by a free-market public policy institute.
Empire Center released its analysis of “unprecedented tax increases” that would come with The New York Health Act, a bill proposed by Assembly Health Committee Chairman Richard Gottfried, D-Manhattan, and Senate Health Committee Chairman Gustavo Rivera, D-Bronx.
Their bill calls funding the health-care program through two new taxes. One would be a graduated payroll tax where companies would pay at least 80 percent of the amount. The other would be a progressive levy placed on income, including capital gains.
Citing figures from the RAND Corporation, the first-year cost for the program would be $157 billion, which would be a 133% increase in state tax receipts.
“In other words, a state with some of the heaviest taxes in the country would be much more than doubling what it collects from individuals and businesses in a single stroke,” the report states.
Empire Center pointed out that the largest tax increase by the federal government was one initiated 80 years ago to help fund the cost of World War II. That 1942 tax increase represented roughly 5 percent of the country’s gross domestic product. A $157 billion tax increase would equate to 8.4 percent of New York’s GDP.
The report notes that some families and businesses would save money, thanks in part to no more out-of-pocket premium expenditures. Roughly two-thirds of New Yorkers would pay less, Empire Center said.
The impact on businesses would vary. Those that currently do not offer insurance to their employees would be faced with paying 80 percent of a payroll tax. Others that provide insurance plans could see their costs go either way, depending on payroll costs.
“Lower-paying chain stores and fast-food enterprises would be more likely to save money,” the report states. “Higher-paying employers – medical practices, law firms, investment companies, high-tech start-ups – would tend to pay more.”
The bills also note that the self-employed would be responsible for 100 percent of the new payroll tax on their income.
The report showed New Yorkers paid the second-highest per capita state and local tax amounts in the U.S. In 2018, that amount was $9,829 – more than 1.8 times the national average of $5,392. Based on Empire Center’s analysis, the per capita rate with a single-payer health-care plan, the tax per capita would nearly double to more than $17,600.
“Switching to a fully government-run, taxpayer-financed health plan would be a profound step no other state has successfully taken,” the report states. “It would affect both the physical health and economic well-being of every New Yorker.”
However, proponents of the health-care for all plan say it’s vital that New York step up and provide insurance for all residents. That includes roughly 1 million residents – and about 150,000 immigrants, according to supporters – who currently go without coverage. For Gottfried, who is retiring from the Assembly after 52 years this year, it’s a cause he’s championed for decades in the legislature.
On Wednesday, supporters rallied in Albany to encourage lawmakers to put the universal health care plan in the state’s budget, which is due to be passed at the end of the month.
“We will be persistent,” Assemblywoman Nathalia Fernández, D-Bronx, said at the event organized by Make the Road NY. “We will knock on that door every day because your life matters. Everybody deserves to be seen and serviced through this budget… Coverage for all is the right thing to do.”
The U.S. State Department and the U.S. National Institute of Allergy and Infectious Diseases (NIAID) were aware in January 2020 that Chinese authorities were withholding COVID-19 data, according to government documents obtained by a legal watchdog organization.
The U.S. National Institutes of Health (NIH) also sent “experts” from the NIH-supported P4 lab at the University of Texas Medical Branch to train Wuhan Institute of Virology technicians in “lab management and maintenance” - nearly two years before the onset of the COVID-19 pandemic - the records obtained by Judicial Watch through a Freedom of Information Act (FOIA) lawsuit show.
Judicial Watch President Tom Fitton said he believes the 90 pages of communication records between the NIH and the Wuhan lab show that Dr. Anthony Fauci’s agency, NIAID, has been “hiding information on China’s failure to provide essential data on COVID-19.”
On Jan. 8, 2020, staff at NIH and NIAID, led by Fauci, circulated an email from the U.S. Embassy in Beijing, “PRC Response to Pneumonia Cases Shows Increased Transparency Over Past Outbreaks, but Gaps in Epidemiological Data Remain.”
“Hi, here is the cable from US Embassy Beijing reporting on the pneumonia outbreak in Wuhan, China. It has ruled out SARS, MERS, and flu. [Redacted] confirmed it is viral infection,” reads an email to colleagues from Dr. Ping Chen, who had been NIAID’s top official in China.
Embassy officials in the email said they were concerned that a “lack of epidemiological data” hindered better risk assessment and response by public health officials.
The officials noted that because of “gaps in [detailed] information” provided by the Chinese regime and “lack of a final confirmed pathogen,” the risk to the United States and global health is “difficult to assess at this time.”
“The flow of official PRC information on this outbreak is limited to that coming from the Wuhan Health Commission and National Health Commission,” the email reads.
“China CDC is referring queries to the three official notices issued to date by the Wuhan Health Commission.”
The first known cases of COVID-19, the disease caused by the CCP (Chinese Communist Party) virus, were reported in December 2019 in Wuhan, China.
“As of January 7, the Wuhan Health Commission has reported 59 local cases of pneumonia with unknown cause,” the email reads.
Workers are seen inside the P4 laboratory in Wuhan, China, on Feb. 23, 2017. (Johannes Eisele/AFP via Getty Images)
Lab technicians from the Wuhan Institute of Virology were also directly trained by NIH-supported experts in April 2018.
“In addition to French assistance, experts from the NIH-supported P4 lab at the University of Texas Medical Branch in Galveston have trained Wuhan lab technicians in lab management and maintenance,” an April 19, 2018, email reads.
“The Wuhan institute plans to invite scientists from the Galveston lab to do research in Wuhan’s lab. One Wuhan Institute of Virology researcher trained for two years at the Galveston lab, and the institute also sent one scientist to U.S. CDC headquarters in Atlanta for six months’ work on influenza.”
Another email between the U.S. Embassy in Beijing and NIH headquarters on Feb. 23, 2018, shows that NIH officials were flagging “China Health News from Chinese Media.”
Among these media reports is an article from state-run outlet Xinhua, “Chinese scientists find how bats carry viruses without getting sick.”
Chinese scientists have identified “bats that harbor highly pathogenic viruses like Ebola, Marburg and SARS coronavirus but do not show clinical signs of disease,” according to the report.
“According to researchers, in humans and other mammals, an immune-based over-response to one of these and other pathogenic viruses can trigger severe illness,” the report reads.
U.S. intelligence officials and numerous experts have obtained evidence suggesting that the CCP virus originated in a lab, but other officials maintain that it originated naturally.
In September 2021, records obtained by The Intercept via a FOIA lawsuit against NIH showed that nonprofit EcoHealth Alliance funneled U.S. funds to scientists at the Wuhan Institute of Virology to research bat coronaviruses.
“The slow-rolling and stonewalling by Fauci’s agency on China, gain of function, and its COVID response generally is pure obstruction,” Fitton said.
NIAID and State Department officials didn’t respond to requests for comment by press time.
Early data from an ongoing clinical trial led by Jefferson Health offers some hope that there may soon be a minimally invasive treatment for loss of smell and taste.
Researchers have developed a topical treatment that uses platelet-rich plasma to restore the senses.
Loss of smell – known as anosmia – and the loss of taste – known as parosmia – are common symptoms of COVID-19. Though they subside for most people infected by the coronavirus, up to 1.5 million U.S. residents continue to have long-term smell and taste disturbances, the researchers said.
Nancy A. Damato, one of the study participants, said losing her senses of smell and taste from COVID was "life changing."
"I felt like I was missing a part of myself and more than anything I missed the experience of gathering with family to enjoy a meal," she said. "Fortunately, the treatments provided by Thomas Jefferson University Hospital are improving my symptoms and showing signs of progress. For the first time in a long time, I have hope for getting my life back to normal."
Platelet-rich plasma, or PRP, can regenerate cells and heal tissue. It has become a common restorative therapy used to treat injured muscles and tendons, increase hair growth and reduce the appearance of scars.
Animal studies have shown PRP also can regenerate cells in the olfactory epithelium – thin, cellular tissue inside the nasal cavity. This tissue is thought to be the site affected by COVID-19-related loss of smell. And since smell and taste are closely linked, the hope is the treatment will improve sense of taste as well.
Some small clinical trials have tested a nasal injectable PRP for smell loss. Though the results were promising, the participants found the injections to be uncomfortable and invasive.
Jefferson Health's topical PRP is considered an less invasive option. The PRP is mixed with a dissolving sponge and applied to the olfactory nerve in the nose via an endoscope. It is a painless procedure.
In a phase I trial, eight patients who had at least six months of olfactory disturbances received monthly applications of the topical PRP for at least three months. Preliminary results show that 50% of the participants experienced significant improvements in smell and taste.
The new treatment also has been provided to additional patients independent of the trial with similarly promising results.
In a phase II study, the researchers plan to look exclusively at patients who developed long-term loss of taste and smell after a COVID-19 infection. This will help them better understand patient variables and the number of treatments needed to provide the most significant improvement.
"It was very important to me and our team to explore less invasive options as this issue has become increasingly prevalent due to COVID-19," said Dr. David Rosen, an otolaryngologist at Thomas Jefferson University Hospital. "The results of phase I of the clinical trial have been promising and we are looking forward to phase II to further improve the treatment."
The treatment is not covered by insurance and costs $500 per application, but it will be available to patients enrolled in the next phase of the clinical study free of charge.
Two Ontario churches that challenged the province's COVID-19 religious gathering restrictions, claiming they violated their right to freedom of religion and assembly under the Constitution, have lost in court.
The Church of God in Aylmer, Ont., and the Trinity Bible Chapel in Waterloo, Ont., were charged in the spring of 2021 for various infringements of the public health restrictions put in place to help curb the spread of the coronavirus that causes COVID-19.
Pomerance writes in her decision that she agrees that religious gathering limits did infringe on the ability of the complainants to engage in religious activity as a congregation, and that the gathering limits had negative impact on the psychological well-being of church members.
"Yet, it remains the fact that, despite the claimants' characterization as such, there was never a complete ban on religious gatherings or religious activity," she concludes.
She explains in her decision that while other means of gathering were not ideal, including periods where outdoor services were allowed or in smaller indoor settings, they need to be understood within the broader context of the pandemic.
"Many sacrifices were required of many individuals and institutions in the interests of public health. Religious institutions were affected, but no more than was reasonably necessary and for no longer than was reasonably required," Pomerance wrote.
Trinity Bible Chapel in Waterloo, Ont., shown on April 25, 2021, was also charged with with various infringements of the public health restrictions. (Hala Ghonaim/CBC)
The justice said she had the benefit of reading the decisions on similar charter challenges brought forward by churches in Manitoba and in British Columbia, where cases were also dismissed. But she says her decision is based solely on the evidence presented to her by the Ontario parties.
Pomerance said she was not tasked with weighing in on whether the law was broken by the Aylmer and Waterloo churches, as they have been charged by other courts.
But she does say in the conclusion of her ruling, that the churches showed a lack of respect when the province was trying to accommodate them by tailoring restrictions and easing them when it was possible to do so.
"Full accommodation of religious freedom would not have resulted in 'legitimate inconvenience' for government. It would have represented a wholesale abdication of government responsibility to act in the public interest. It would have meant turning a blind eye to threat of severe health consequences for a large swath of the population."
When reached for comment Wednesday, the lawyer representing the Church of God and Trinity Bible Chapel said she and her client are reviewing the decision to determine whether to appeal.
"We are, of course, disappointed with the decision in this case. For nearly two years now, considerable deference has been given to governments across the country by the courts, allowing them to impose restrictions on the Charter-guaranteed rights and freedoms of Canadians seemingly without limit," said Lisa D.S. Bildy in an email to CBC News.
To sayhand sanitizermade headlines in 2020 is an understatement. As consumerssnapped up every bottlein the early days of the COVID-19 pandemic, Kayla Ivey set to work. Ivey is a product development scientist at GOJO Industries, where she is lead formulator for the Purell brand of hand sanitizer. The company activated its demand-surge preparedness team in December 2019, in response to news of pneumonia caused by a virus that we now know as SARS-CoV-2. Over subsequent months, the companyresponded to staggering demandby activating about 230,000 m2of manufacturing space, adding multiple new facilities, and hiring over 500 additional employees.
Credit: Amanda Hemstreet Photography
Meanwhile, Ivey took on more projects than ever, including launching multiple new hand sanitizer products. In August 2021, she introduced herself on Twitter using #BlackinChemRollCall─a hashtag for Black scientists to talk about their expertise and their journey in chemistry─and shared photos of two products she had developed. The tweet generated thousands of likes and scores of appreciative comments.
Carmen Drahl talked with Ivey about her work and how she has used her newfound soapbox. This interview was edited for length and clarity.
What general components make up hand sanitizer, and what’s the purpose of each?
The main component is the active ingredient, the thing that’s actually doing the germ-killing. In our sanitizer, it’s mostly ethanol. The US Food and Drug Administration sets the minimum concentration of ethanol in hand sanitizers at 60%. Because the sanitizer is mostly ethanol, we need a denaturant to make the product undesirable to consume. There are a couple of options; isopropyl alcohol is typically used as the denaturant in Purell sanitizers.
For our gel sanitizers, we have gelling agents, usually water-soluble polymers. For the foam sanitizers, we have foaming agents, usually a water-soluble surfactant. The rest of the formula is mostly skin moisturizers.
Tell me how the early days of the pandemic unfolded for you.
The company ramped up manufacturing starting in January 2020. I remember having a meeting about the ramp-up at the end of that January, but at the time I didn’t think it was that big a deal. It seems silly now to say that I didn’t realize what the impact was going to be. I went to Niagara Falls; I came back March 8, 2020. Not long after getting back from my vacation─boom, we’re working from home. During the last week of April, I was called into a meeting and given six formulation projects. The pandemic definitely elevated the use of hand sanitizer, and these new products met consumers’ preferences for formulation and usage.
That’s when I realized that sanitizer, and Purell specifically, was going to be thrust into the spotlight. In a normal year, I would only have two or three projects, and usually we give ourselves 1–2 years for each one. Getting six new projects and being told that almost all of them needed to be launched within the next 6–9 months was a little wild.
What was it like for your #BlackInChemRollCall tweet to, if you’ll pardon the expression, go viral?
In 2020 I tweeted something very similar, and it got some likes. But in 2021 almost the exact same tweet went a lot further. It was kind of shocking. I tweeted it and just went about my day. When I checked back, I saw a text from my uncle, who said, “Did you know your tweet’s going crazy?” I think something that helped with the second tweet is that by that point, two new hand sanitizers I’d launched were on shelves. One of those, the moisturizing two-in-one product, was a project I got at that April 2020 meeting. You could buy both products on Amazon, and I was the formulator who made them. Some people were responding to the tweet to say, “I just bought this yesterday. That’s so cool that you made this!”
Ivey developed two new formulations of Purell hand sanitizer, launched in 2020 and 2021, an extra-strength formulation with 85% ethanol instead of the more typical 70%, and another with a blend of moisturizing ingredients. Credit: GOJO Industries
How have you been using Twitter to encourage Black excellence in chemistry?
Because of that tweet, teachers and professors have invited me to speak to their high school and college chemistry classes. One of the main things I try to get across is how far you can go with a bachelor’s degree, like me. Then I bring in friends with advanced degrees to show how far you can go with your master’s or your PhD.
My transition to getting hired at GOJO was pretty seamless, because the company already had a relationship with my university. I was hired a week after I graduated. After starting at GOJO, I met scientists in advanced roles who only had a bachelor’s degree, and I realized that I could work my way up. I’ve been here ever since, and I’ve been able to move around within the company.
Also, it wasn’t until I got to college that I found out that a lot of science PhD programs are funded and that you can actually get a stipend. I think some people are discouraged about even going into grad school for science because they think they have to fork over the money for it. So something I try to do is let students know that there’s a lot more at their fingertips than they think.
What has working through these unprecedented times taught you about yourself?
It taught me that I easily adapt to change, more than I thought I could. It pushed me out of my comfort zone.
The structure of working from home and social distancing helped me become a better bench chemist. We had to reserve lab time to make sure that there wouldn’t be too many people in the lab at once. Since I was working on sanitizer, I could in theory kick someone out if I wanted to, but I didn’t do that.
When I was home, I did a lot of ideation before going into the lab, to make my lab time run as smoothly as possible. I did a lot more paper exercises and research with my laptop. I’m a lot more confident in my abilities. I was able to make a final product with fewer iterations along the way, which as a chemist is very exciting.
China’s aggressive “zero COVID” strategy has served it remarkably well. The country has reported fewer than 154,000 cases and 5200 deaths from COVID-19 so far, a tiny fraction of the figures in the United States. But as the highly transmissible Omicron variant seeps into the country and the social and economic costs of the zero COVID policy mount, Chinese researchers are examining options for coexisting with the virus, as the rest of the world is doing. Some think that shift may soon begin.
It will be a momentous decision, and the country is sure to proceed cautiously. China wants to avoid COVID-19 outbreaks like the one now overwhelming Hong Kong, which reported more than 34,000 new COVID-19 infections and 87 deaths on 28 February alone. Modeling by researchers at the University of Hong Kong (HKU) predicts that toll will climb rapidly. Yanzhong Huang, a global health specialist at the Council on Foreign Relations, a U.S. think tank, says until recently he believed China might introduce more flexible measures as early as this month. Now, “It is very likely that Chinese leaders may wait till the dust settles” from the Hong Kong crisis, he says. Xi Chen, a public health scientist at the Yale School of Public Health, says China needs more time—up to 1 year—to further raise vaccination and booster coverage, especially among the elderly, and bolster rural health care capabilities.
China’s zero COVID policy has relied on mass testing, contact tracing, isolating the infected, restrictions on international and domestic travel, and lockdowns of entire cities. The system has helped China stamp out every outbreak so far, including several of the Omicron variant since mid-January. But outbreaks are becoming more frequent and widespread. On 25 February, the National Health Commission reported 93 confirmed cases of local transmission in 10 provinces, despite the burdensome countermeasures. Shenzhen, which borders Hong Kong, recently closed museums, libraries, many parks, and beaches in response to an uptick in cases. Apartment compounds face lockdowns if even one resident tests positive. Most people must get tested every 48 hours.
“The huge inconveniences and difficulties imposed upon people’s livelihoods and lifestyles may be turning the wheels of the Chinese policy machinery to consider some kind of policy adjustment,” China political analyst Chen Gang of the National University of Singapore (NUS) wrote in a February commentary for Channel News Asia. And COVID-19 countermeasures started to dent China’s economic growth in the second half of 2021, says Lu Xi, an NUS specialist in Chinese economic policy. “All of the economic indices point to a continued decline,” Lu says. “There will likely come a point when the costs [of zero COVID] outweigh the benefits,” says Zhangkai Cheng, a respiratory specialist at Guangzhou Medical University. “Whether that point has arrived is up for debate.”
Under what’s now called “dynamic zero COVID,” localities have leeway to “tailor the measures to local conditions,” says HKU virologist Huachen Zhu. But the national government is pushing back at what it considers unnecessary local restrictions. On 18 February, the National Development and Reform Commission, which manages economic affairs, told local governments to avoid arbitrary lockdowns and barred unauthorized closures of restaurants, supermarkets, tourist sites, and cinemas. The Chinese Center for Disease Control and Prevention is studying changes to existing control measures to “ensure normal international exchanges and economic development,” its chief epidemiologist, Zunyou Wu, said at a 15 February forum in Beijing.
But the situation in Hong Kong shows why caution is needed. The semiautonomous city of 7.4 million followed its own zero COVID approach that eschewed citywide lockdowns. It worked relatively well through December 2021, but with the arrival of the Omicron variant, cases have soared, in a population where many vulnerable people have not been immunized. Although vaccination coverage overall is at 76%, only 46% of people in their 70s and 29% of those in their 80s were fully vaccinated. Many elderly were alarmed by early reports of side effects and felt confident in the city’s ability to keep the virus at bay. Deaths are concentrated among those who shunned vaccination, says HKU virologist Jin Dong-Yan.
The city now plans to test every resident three times in March to identify cases and may resort to limited or even citywide lockdowns. But HKU modeling suggests things will get worse before they get better. If social distancing measures stay the same—meaning restaurants stop serving after 6 p.m. and gyms, bars, and hair salons are closed—4.6 million Hong Kong residents will have been infected by mid-May, the models suggest. More than 3200 will have died.
Epidemiologists say China, too, will face a wave of infections during any transition. In places that lack community health clinics or general practitioners, even those with mild symptoms are likely to rush to hospitals, and “medical resources will quickly be exhausted,” Lu says. Although the vaccination rate now tops 87%, and more than 550 million people have received boosters, vaccination of the elderly lags, especially in rural areas. And with many Chinese vaccines relying on inactivated virus rather than the messenger RNA technology common in the West, it’s unclear how fast their protection wanes or how well they will fare against new variants, says immunologist Rustom Antia of Emory University.
Given the high stakes, many predict China’s leaders will proceed cautiously. Huang envisions steps such as reducing the length of quarantines and putting fewer contacts into isolation. Yale’s Chen thinks China might first open up one city or region as a test case.
China’s big leap may affect the rest of the world as well. Unleashing COVID-19 on a population of 1.4 billion means a lot of people “will be brewing the virus,” says Gabriel Leung, HKU’s dean of medicine. That will provide ample opportunity for new variants to emerge. “It’s not just a national problem, it’s actually a global issue,” Leung says.
It takes Lawrence Tabak about 15 minutes to rattle off all the potential COVID-19 treatments being tested in the clinical trial programme he oversees: a lengthy, tongue-twisting list that includes drugs to disarm the virus, to soothe inflammation and to stop blood clots. Over the past two years, the ACTIV programme, run by the US National Institutes of Health (NIH), has included more than 30 studies — 13 of them ongoing — of therapeutic agents chosen from a list of 800 candidates. Several of the studies are due to report results in the first half of the year.
And that’s just in his programme; hundreds more are in progress around the world. Whether those results are positive or negative, Tabak says, 2022 is poised to provide some much-needed clarity on how best to treat COVID-19. “The next three to four months are, we hope, going to be very exciting,” says Tabak, acting director of the NIH in Bethesda, Maryland. “Even when a trial does not show efficacy, that’s still incredibly important information. It tells you what not to use.”
Nearly two years into the pandemic, that information is still badly needed: with more than one million new infections and thousands of deaths around the world each day, COVID-19 continues to strain health-care systems and exact a terrible human toll. Researchers have developed a handful of options — including two oral antiviral drugs, Paxlovid and molnupiravir, authorized in some countries in the past couple of months — that help in certain situations. But gaps remain, and researchers think that this year will bring new drugs and new uses for older drugs, including better treatments for mild COVID-19.
And although vaccines remain the most important way to rein in the pandemic, there is still a desperate need for better therapies to treat people who cannot — or choose not to — access the vaccines, whose immune systems cannot respond fully to vaccination, or who experience breakthrough infections. “The main tool in combating the pandemic is prevention, and the main tool in prevention is vaccination,” says Taher Entezari-Maleki, who studies clinical pharmacy at Tabriz University of Medical Sciences in Iran. “But new medications can fill in when vaccines do not work — for example against new variants.”
Over time, researchers have ramped up clinical-trial infrastructure, and repeated surges of the coronavirus SARS-CoV-2 have ensured a ready pool of potential study participants. The result has been an accelerated drug pipeline, says Tabak (see ‘Bursting pipeline’). “It has been two years, which feels like a long time for everybody,” says Paul Verdin, head of consulting and analytics at the London-based pharmaceutical analytics firm Evaluate. “But in the grand scheme of drug development, that’s not very long.”
Source: BIO COVID-19 Therapeutic Development Tracker
Trickle becomes flood
Early in the pandemic, much research focused on finding ways to treat people who were seriously ill with COVID-19, to save lives and ease pressures on hospitals. In mid-2020, scientists found that a steroid called dexamethasone tamps down supercharged immune responses that can contribute to late stages of severe disease, and reduces deaths in people in this group1. Such steroids remain the most effective treatments for reducing COVID-19 deaths.
Other drugs target the virus more directly but must be administered by medical professionals, limiting their use. The antiviral drug remdesivir (Veklury), made by Gilead Sciences in Foster City, California, is given as an infusion, and so was reserved, until recently, only for people hospitalized with COVID-19. (On 21 January, the US Food and Drug Administration (FDA) authorized remdesivir for outpatient treatment of people at high risk of COVID-19 complications.)
Several firms have developed monoclonal antibodies — mass-produced versions of the neutralizing antibodies that the immune system pumps out to bind to and disable SARS-CoV-2. These therapies offered another early route to treatment, and more than 200 monoclonal antibodies are now under development or authorized. But they are expensive compared with other treatments, are in short supply, and often have to be infused. One recent exception is a long-lasting combination of two monoclonal antibodies, called Evusheld. This drug, made by AstraZeneca in Cambridge, UK, can be injected into muscle, and was authorized by the FDA last December for prevention of COVID-19 in people at high risk of exposure to SARS-CoV-2.
With time, the focus began to shift to drugs that could be used outside a hospital setting to treat mild illness, in the hope of preventing progression to more severe disease. In late 2021, two antiviral treatments — Lagevrio (molnupiravir), developed by Merck, based in Kenilworth, New Jersey, and Ridgeback Biotherapeutics in Miami, Florida; and Paxlovid (a combination of two drugs, nirmatrelvir and ritonavir), developed by Pfizer, based in New York City — became available as pills that could be taken at home.
Neither drug is a panacea, notes José Carlos Menéndez Ramos, who studies pharmacy at the Complutense University of Madrid. A laboratory study2 has suggested that molnupiravir might be able to cause mutations in human DNA, leading regulators to advise against its use during pregnancy. Some countries, including France and India, have chosen not to authorize it. And Paxlovid’s use could be limited because it might interact with a wide range of commonly used medications.
A nurse administers a monoclonal-antibody treatment at a mobile clinic in Detroit, Michigan last December.Credit: Kimberly P. Mitchell/Detroit Free Press/TNS/ZUMA/eyevine
Luckily, the two could soon have company. Many antivirals in trials target one of two key viral proteins, with the aim of stopping the virus from replicating. Like molnupiravir, some of these target a protein called RNA-dependent RNA polymerase. About 40 candidates are under development, says Chengyuan Liang, who studies pharmacy at Shaanxi University of Science and Technology in Xi’an, China. Another roughly 180 molecules act like Paxlovid and block the SARS-CoV-2 main protease protein, which is responsible for clipping viral proteins into their final, functional forms. Of these protease inhibitors, the one that has progressed furthest is S-217622, made by Shionogi in Osaka, Japan, which is in late-stage clinical trials.
Other antiviral medications with a fresh set of targets are working their way along the pipeline. Some of them have been selected to block the human proteins that SARS-CoV-2 uses to infiltrate cells, rather than viral proteins. For example, a cancer drug called plitidepsin targets a human protein called eEF1A, which is involved in making proteins and is important for the replication of several viral pathogens. Plitidepsin has been shown to reduce SARS-CoV-2 replication in mice3, and is now in phase III clinical trials.
Targeting human proteins such as eEF1A could make it more difficult for the virus to mutate to evade the drug than when viral proteins are the target, says Ramos. “On the flip side, targeting a host protein can lead to toxicity,” he adds. In the case of plitidepsin, Ramos is hopeful that the dose required to restrict SARS-CoV-2 replication is low enough, and treatment duration short enough, for the drug to be a safe antiviral.
Researchers hope to target a smattering of other viral and human proteins important for SARS-CoV-2 replication. For example, the drug camostat, made by Ono Pharmaceutical in Osaka, inhibits a human protease, called TMPRSS2, that SARS-CoV-2 and several other coronaviruses use to enter human cells. Camostat is already used in Japan to treat non-viral conditions such as pancreatitis.
New combinations
Some familiar COVID-19 antivirals could find fresh uses, either in a formulation that makes them easy to administer, or in different patient groups. Antivirals such as remdesivir seem to work best when given earlier in the course of infection, before severe disease sets in; researchers are working on oral formulations to see whether this definitely is the case.
Conversely, researchers also want to know whether the new oral antivirals could improve outcomes for people with severe COVID-19. Clinical trials of molnupiravir in people who have been hospitalized have suggested4 that these drugs would not work against moderate or severe illness, when the immune system is contributing to the damage. But epidemiologist and infectious-disease specialist Peter Horby at the University of Oxford, UK, says that the studies of people in hospital might have been too small for researchers to draw a firm conclusion. It’s a common problem during the pandemic, he says: many investigators launched quick, small trials, enrolling too few participants to yield clear answers. Some treatments were abandoned prematurely. “The studies weren’t big enough, and stuff was being ditched way too early in our opinion,” he says.
Horby is one of the lead investigators on the UK RECOVERY trial — a large, multitherapy trial in people hospitalized with COVID-19. RECOVERY will test molnupiravir and eventually Paxlovid, he says. Treating sicker people could be the best way to make the most of these scarce drugs. Most infected people won’t develop severe disease and there is no definitive way to tell who will; giving the drug to people with mild disease might not yield as much benefit as treating those who are severely ill. While supplies of the drugs are low, he says, “you’ve got to target your use of a limited and expensive resource”.
The RECOVERY trial will also begin to unpick whether these antivirals work synergistically when given together. Some participants in the trial will receive one of the drugs; others might receive a combination of the two, or one of the antivirals together with a monoclonal antibody. Researchers hope that combining antivirals can boost their effectiveness and reduce the chances that the virus will develop resistance to the drugs. “We don’t have many antiviral options,” says Horby. “If we lost any, it would be a disaster.”
Researchers are exploring other options for those hospitalized with COVID-19. Treatments at this late stage often focus on the immune system, which, whipped into a frenzy by the viral infection, can begin to harm the body’s own tissues. Anti-inflammatory drugs are top of the list. RECOVERY is now looking at higher doses of steroids such as dexamethasone, and several trials are studying whether diabetes drugs called SGLT2 inhibitors — also thought to have anti-inflammatory properties — help people with moderate to severe COVID-19.
Reuse and repurpose
Globally, some of the most important trials are those that study widely available drugs developed to treat other diseases. For Philippe Guérin, director of the Infectious Diseases Data Observatory at the University of Oxford, it has been frustrating to see that many large clinical trials are focused on therapies that, in a lot of countries, will be too expensive to buy or too difficult to administer. “There is a clear disconnect between the needs of lower- to middle-income countries and the level of research,” he says. “Most of the large funding was focused on the needs of high-income countries.”
A health-care worker tests samples from people with COVID-19 as part of the ANTICOV trial.Credit: Kenny Mbala/DNDi
This was reflected in the early attention given to people with severe COVID-19, who were coming to hospitals and being treated in intensive care units (ICUs). “In low-income countries, you don’t have ICU capacity,” says Guérin. “What you want to do is try to prevent the non-severe patients from becoming severe, and that was not clearly the priority of the funders.”
Much of the early research on treating mild COVID-19 focused on monoclonal antibodies, notes public-health specialist Borna Nyaoke, clinical operations representative for East Africa at the Drugs for Neglected Diseases initiative, a non-profit organization in Nairobi. But these drugs pose a challenge in lower- and middle-income countries, she says, because of their cost, and because they need to be stored at low temperatures and administered by trained medical personnel. And the newer, oral antivirals promise to be less expensive, but are still in short supply.
For more practical solutions, Nyaoke looks to the ANTICOV trial, which is enrolling participants in 19 sites across 13 countries in sub-Saharan Africa. The trial is looking at a range of repurposed treatments, including the anti-parasitic drug ivermectin; an inhaled steroid called budesonide; and the antidepressant fluoxetine. (Other trials, including one run by ACTIV, are testing a similar antidepressant, called fluvoxamine, which has shown promise in some early clinical trials.)
Some of these treatments have already been tested — and sometimes failed — in smaller clinical trials. Ivermectin, in particular, has become a popular but controversial COVID-19 treatment in many countries, despite clinical trials indicating that the drug does not work as an antiviral in early stages of infection. Both ACTIV and ANTICOV are testing the treatment anew. ACTIV is running a trial in people with mild to moderate COVID-19, and results are due in the next few months. “No matter what we find, that will be of interest to many people,” says Tabak. The ANTICOV trial will test ivermectin for its potential anti-inflammatory properties in people seriously ill with COVID-19, and will combine it with an antimalarial drug. Preclinical data have been promising, says Nyaoke. “Combining drugs with different mechanisms of action increases a treatment’s chances of success,” she says.
Drug developers still face challenges when it comes to finding COVID-19 therapies. For instance, there is a shortage of non-human primates to use for research, and the costs of animals have skyrocketed, says Liang.
And although clinical-trial planners are not short of participants, running a trial in a pandemic is complicated: emerging viral variants can change the spectrum of symptoms, the severity of disease and the population that’s most affected. In some cases, variants have rendered COVID-19 therapies — particularly some of the monoclonal antibodies — obsolete. By contrast, broader-acting drugs such as remdesivir, which was developed in 2015 and tested against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in animal models, and against Ebola in humans, could be useful tools in future pandemics. In the middle of this chaos, it’s hard to know which of the many therapies in current trials will be successful, says Verdin. “The whole thing is such a big churning bubble; the goal posts are constantly moving,” he says. “It’s very difficult to pick a winner.”
