Cleaning has taken on a whole new meaning in Frank Mosco's household during the COVID-19 pandemic. There's a protocol for everything he and his two teenage daughters do.
Experts agree that over-disinfecting is better than inadequate disinfecting, especially during a pandemic.
"We wipe down every package that comes into the house and the items inside," says Mosco, a technologist and social justice activist in Hastings-on-Hudson, N.Y. "If it's a fruit or vegetable, I use vinegar and water, or water and soap. Then we throw out the boxes, clean up the table, and wash our hands." Only then do they put items away.
As the novel coronavirus continues to pose an invisible threat, parents of infants to adolescents are pondering how vigorously and frequently to clean and disinfect surfaces at home and apply hand sanitizer in public. They also fret over whether there can be too much of a good thing: Will making everything as seemingly germ-free as possible reduce immunity down the road?
Experts agree that over-disinfecting is better than inadequate disinfecting, especially during a pandemic. Every family should assess their particular risks. Factors to consider include pre-existing medical conditions, the number of people living in the same home, and whether anyone works in a hospital or other virus-prone environment, says Kari Debbink, assistant professor of biology at Bowie State University in Bowie, Maryland.
Constantly cleaning everything in sight isn't necessary, she explains, because coronavirus tends to spread mainly via immediate contact with respiratory droplets—catching it from surfaces is a less-likely scenario. The longer the virus stays on a surface, the less contagious it becomes.
Some parents worry that their children's growing bodies may become accustomed to an environment that is "too clean." Debbink, a virologist, offers a salient reminder: "The immune system comes into contact with many, many different antigens every day, and it is 'trained' from birth onwards to respond to pathogens. Doing a little more cleansing and disinfecting during the pandemic will not weaken the immune system."
Other experts agree. "There should be no negative outcome to properly washing your hands more frequently," says Stacey Schultz-Cherry, an infectious diseases specialist at St. Jude Children's Research Hospital in Memphis, Tennessee. "Even with enhanced disinfection, kids are still getting exposed to immune-boosting microbes from playing outside, having pets, etc."
"There's no reason why hand sanitizer would weaken anyone's immune system of any age."
Applying hand sanitizer consisting of at least 60 percent alcohol helps clean hands while outdoors, says Angela Rasmussen, associate research scientist and a virologist at Columbia University's Mailman School of Public Health in New York. "There's no reason why hand sanitizer would weaken anyone's immune system of any age," she adds, and recommends moisturizer so hands don't dry out from frequent use. Meanwhile, "cleaning and disinfecting at home also don't have an impact on antiviral immunity, in kids or adults."
With the coronavirus foremost in parents' minds, Patricia Garcia, a pediatric hospitalist, has fielded many questions about how thoroughly they should wipe, rub, scrub, or mop. As medical director of Connecticut Children's Healthy Homes Program in Hartford, which takes aim at toxins and other housing hazards, she reassures them with this mantra: "You're never going to get it perfectly sterilized, and that's okay."
To quell some of these concerns, in March the U.S. Environmental Protection Agency (EPA) released a list of products for household use. None of these products have been specifically tested against SARS-CoV-2, the novel coronavirus that causes COVID-19. But the agency expects these products to be effective because they have demonstrated efficacy against a different human coronavirus similar to SARS-CoV-2 or an even harder-to-kill virus.
Many products on the list contain isopropyl alcohol or hydrogen peroxide. "When using an EPA-registered disinfectant," the agency's website instructs, "follow the label directions for safe, effective use. Make sure to follow the contact time, which is the amount of time the surface should be visibly wet."
Bear in mind that not all cleaners actually disinfect, cautions Alan Woolf, a pediatrician at Boston Children's Hospital who directs its environmental health center and is a professor at Harvard Medical School. Some cleaners remove visible dirt, grease, and grime, but they don't kill viruses. Disinfectants by their nature inactivate both bacteria and viruses. "That's an important distinction," Woolf says.
Frequently touched surfaces—for instance, doorknobs, light switches, toilet-flushing levers, and countertops—should not only be cleaned, but also disinfected at least daily during a pandemic if someone in the household is sick. The objects one touches upon coming home are the ones most likely to become contaminated with viruses, experts say.
Before bringing items inside, "it might be good to clear off a counter space where they will be placed," says Debbink, the biology professor and virologist. "This way, they come into contact with as few items and surfaces as possible."
If space permits, another option would be to set aside nonperishable items. "I've heard of some families putting things in a 'mud room' and closing the door for 48 hours, some leaving things in their garage or car trunk," says Stephanie Holm, co-director of the Western States Pediatric Environmental Health Specialty Unit at the University of California, San Francisco. "Letting new purchases sit for 48 hours undisturbed would greatly reduce the number of viable viruses present."
Cleaning surfaces is recommended before disinfecting them. Holm suggests using unscented soap and microfiber cloths instead of paper towels, which can transmit bacteria and viruses from one area to another.
Soap has the power to eradicate viruses with at least 20 seconds of contact time. It attacks the coronavirus's protective coat, explains infectious diseases specialist Schultz-Cherry. "If you destroy the coat, the virus is no longer infectious. Influenza virus is also very sensitive to soap."
"The most important thing that parents should do for children's immune systems is make sure they are up to date on all their vaccines."
For cribs, toys, and other mouth-contact surfaces, sanitizing with soap and water, not disinfectants, is advisable, says pediatrician Woolf. Fresh fruits and vegetables also can be cleaned with soap, removing dirt and pesticide residue, he adds.
"Some parents are nervous about using disinfectant on toys, which is understandable, considering many toys end up in children's mouths, so soap and water can be an alternative," says pediatrician Garcia, who recommends using hot water.
While some toys can go in the washing machine and dryer or dishwasher, others need to be cleaned by hand, with dish soap or a delicate detergent, as indicated on their labels. But toys with electrical components cannot be submerged in water, in which case consulting the EPA's list of disinfectants may be a parent's best option, she says.
Labels on the back of cleaning and disinfecting products also contain specific instructions. Not allowing a liquid to sit on a surface for the recommended time results in exposure to chemicals without even accomplishing the intended purpose of disinfection. For most household bleach-containing agents, the advisable "dwell time" is 10 minutes. "Many people don't realize this," says Holm, the environmental health specialist who also trained as a physician.
Beware of combining any type of cleaners or disinfectants that aren't already premixed. Doing so can release harmful gases into the air, she cautions.
During the pandemic, Mosco and his daughters have been very conscientious about decontaminating whatever comes through their doors. Mosco says he doesn't believe the family is overusing cleaning and disinfecting products. Although he's fastidious, he says, "a completely sterile environment is not the goal."
His mother, who was a nurse, instilled in him that exposure to some bacteria is a good thing. In turn, he "always encouraged his kids to play with animals, and to have fun in sand and dirt, with plenty of sunlight to keep their immune systems strong."
Even though a vaccine for coronavirus currently doesn't exist, parents can take some comfort in the best weapon available today to protect kids from deadly pathogens: "The most important thing that parents should do for children's immune systems," says virologist Rasmussen, "is make sure they are up to date on all their vaccines."
In October 2006, Craig Mello received a strange phone call from Sweden at 4:30 a.m. The voice at the other end of the line told him to get dressed and that his life was about to change.
"We think this could be effective in [the early] phase, helping the body clear the virus and preventing progression to that severe hyperimmune response which occurs in some patients."
Shortly afterwards, he was informed that along with his colleague Andrew Fire, he had won the Nobel Prize in Physiology or Medicine.
Eight years earlier, biologists Fire and Mello had made a landmark discovery in the history of genetics. In a series of experiments conducted in worms, they had revealed an ancient evolutionary mechanism present in all animals that allows RNA – the structures within our cells that take genetic information from DNA and use it to make proteins – to selectively switch off genes.
At the time, scientists heralded the dawn of a new field of medical research utilizing this mechanism, known as RNA interference or RNAi, to tackle rare genetic diseases and deactivate viruses. Now, 14 years later, the pharmaceutical company Alnylam — which has pioneered the development of RNAi-based treatments over the past decade — is looking to use it to develop a groundbreaking drug for the virus that causes COVID-19.
"We can design small interfering RNAs to target regions of the viral genome and bind to them," said Akin Akinc, who manages several of Alnylam's drug development programs. "What we're learning about COVID-19 is that there's an early phase where there's lots of viral replication and a high viral load. We think this could be effective in that phase, helping the body clear the virus and preventing progression to that severe hyperimmune response which occurs in some patients."
Called ALN-COV, Alnylam's treatment hypothetically works by switching off a key gene in the virus, inhibiting its ability to replicate itself. In order to deliver it to the epithelial cells deep in the lung tissue, where the virus resides, patients will inhale a fine mist containing the RNAi molecules mixed in a saline solution, using a nebulizer.
But before human trials of the drug can begin, the company needs to convince regulators that it is both safe and effective in a series of preclinical trials. While early results appear promising - when mixed with the virus in a test tube, the drug displayed a 95 percent inhibition rate – experts are reserving judgment until it performs in clinical trials.
"If successful this could be a very important milestone in the development of RNAi therapies, but virus infections are very complicated and it can be hard to predict whether a given level of inhibition in cell culture will be sufficient to have a significant impact on the course of the infection," said Si-Ping Han, who researches RNAi therapeutics at California Institute of Technology and is not involved in the development of this drug.
So far, Alnylam has had success in using RNAi to treat rare genetic diseases. It currently has treatments licensed for Hereditary ATTR Amyloidosis and Acute Hepatic Porphyria. Another treatment, for Primary Hyperoxaluria Type 1, is currently under regulatory review. But its only previous attempt to use RNAi to tackle a respiratory infection was a failed effort to develop a drug for respiratory syncytial virus (RSV) almost a decade ago.
However, the technology has advanced considerably since then. "Back then, RNAi drugs had no chemical modifications whatsoever, so they were readily degraded by the body, and they could also result in unintended immune stimulation," said Akinc. "Since then, we've learned how to chemically modify our RNAi's to make them immunosilent and give them improved potency, stability, and duration of action."
"It would be a very important milestone in the development of RNAi therapies."
But one key challenge the company will face is the sheer speed at which viruses evolve, meaning they can become drug-resistant very quickly. Scientists predict that Alnylam will ultimately have to develop a series of RNAi drugs for the coronavirus that work together.
"There's been considerable interest in using RNAi to treat viral infections, as RNA therapies can be developed more rapidly than protein therapies like monoclonal antibodies, since one only needs to know the viral genome sequence to begin to design them," said David Schaffer, professor of bioengineering at University of California, Berkeley. "But viruses can evolve their sequences rapidly around single drugs so it is likely that a combinatorial RNAi therapy may be needed."
In the meantime, Alnylam is conducting further preclinical trials over the summer and fall, with the aim of launching testing in human volunteers by the end of this year -- an ambitious aim that would represent a breakneck pace for a drug development program.
If the approach does ultimately succeed, it would represent a major breakthrough for the field as a whole, potentially opening the door to a whole new wave of RNAi treatments for different lung infections and diseases.
"It would be a very important milestone in the development of RNAi therapies," said Han, the Caltech researcher. "It would be both the first time that an RNAi drug has been successfully used to treat a respiratory infection and as far as I know, the first time that one has been successful in treating any disease in the lungs. RNAi is a platform that can be reconfigured to hit different targets, and so once the first drug has been developed, we can expect a rapid flow of variants targeting other respiratory infections or other lung diseases."
The Biggest Challenge for a COVID-19 Vaccine
Although no one has conducted a survey on the topic, it's safe to say that a single hope unites much of humanity at the present moment: the prospect of a vaccine for COVID-19, which has infected more than 9 million people worldwide, killed nearly 500,000, and sent the global economy into a tailspin since it first appeared in China last December.
"We've never delivered something to every corner of the world before."
Scientists are racing to make that vision a reality. As of this writing, 11 vaccine candidates are in clinical trials and over 100 others are in preclinical development, in a dozen countries. Pointing to new technology and compressed testing protocols, experts predict a winner could emerge in 12 to 18 months—a fraction of the four years it took to develop the previous record-holder, the mumps vaccine, in the 1960s. Teams at Oxford University and Boston-based Moderna Therapeutics say they could have a product ready even sooner, if the formulas they're testing prove safe and effective. A just-announced White House initiative, Operation Warp Speed, aims to fast-track multiple candidates, with the goal of delivering 100 million doses in November and another 200 million by January 2021.
These timetables could prove wildly over-optimistic. But even if the best-case scenario comes true, and a viable COVID-19 vaccine emerges this fall, a gargantuan challenge remains: getting the shot to everyone who needs it. Epidemiologists figure that at least 70 percent of Earth's population—or 5.6 billion people—would have to be inoculated to achieve "herd immunity," in which each person who catches the disease passes it to less than one other individual. "In order to stop the pandemic, we need to make the vaccine available to almost every person on the planet," Microsoft co-founder Bill Gates blogged in April, as his foundation pledged $300 million to the effort. "We've never delivered something to every corner of the world before."
The difficulties are partly logistical, partly political, and largely a combination of the two. Overcoming those obstacles will require unprecedented cooperation among national governments, international organizations, and profit-minded corporations—in an era when nationalist rivalries are rampant and global leadership is up for grabs.
That may be tougher than developing the vaccine itself.
Logistical Conundrums
Manufacturing and distributing billions of vaccine doses would be a daunting task even in the most harmonious of times. Take the packaging problem. The vaccines under development range from old-school (based on inactivated or weakened viruses) to cutting-edge (using snippets of RNA or DNA to train the immune system to attack the invader). Some may work better than others for different patient groups—the young versus the elderly, for example. All, however, must be stored in vials and administered with syringes.
Among the handful of U.S. companies that manufacture such products, many must import the special glass tubing for vials, as well as the polypropylene for syringe barrels and the rubber or silicone for stoppers and plungers. These materials are commonly sourced from China and India, where lockdowns and export bans restrict supply. Rick Bright, the ousted director of the federal Biomedical Advanced Research and Development Authority (BARDA), claims he was ignored when he warned the Trump Administration that a medical-glass shortage was looming before the coronavirus crisis hit; securing enough to vaccinate 300 million Americans, he told Congress in May, could take up to two years.
Getting the vaccine to poorer countries presents further hurdles. To begin with, there's refrigeration. Inactivated or live vaccines must be kept between 2 and 8 degrees Centigrade (or 35 to 46 degrees Fahrenheit); RNA vaccines typically require much colder temperatures—as low as -80 degrees. This makes storage and transport challenging in parts of the world that lack reliable electricity. DNA vaccines don't need cold storage, but (like RNA vaccines) they remain experimental. They've never been approved to treat any human disease.
Tracking vaccine distribution is another conundrum for low- to-middle-income countries. "Supply chain management is really about information," explains Rebecca Weintraub, assistant professor of global health and social medicine at Harvard Medical School and director of the Better Evidence project at Harvard's Ariadne Labs. "It's about leveraging data to determine demand, predict behavior, and understand the flow of the product itself." Systems for collecting and analyzing such data can be hard to find in poorer regions, she notes. What's more, many people in those areas lack any type of ID card, making it difficult to know who has or hasn't received a vaccine.
Weintraub and two coauthors published an article in April in the Harvard Business Review, suggesting solutions to these and other developing-world problems: solar direct-drive refrigerators, app-based data-capture systems, biometric digital IDs. But such measures—not to mention purchasing adequate supplies of vaccine—would require massive funding.
And that's where the logistical begins to overlap with the political.
Global Access Versus "Vaccine Nationalism"
An array of institutions have already begun laying the groundwork for achieving worldwide, equitable access to COVID-19 vaccines. In February, the World Bank and the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) cohosted a global consultation on funding vaccine development and manufacturing. In late April, the World Health Organization (WHO), in collaboration with dozens of governments, nonprofits, and industry leaders, launched a program called the Access to COVID-19 Tools Accelerator to expedite such efforts.
Soon afterward, the European Union, along with six countries and the Bill and Melinda Gates Foundation, held a Coronavirus Global Response telethon that raised $8 billion to support Gavi, the Vaccine Alliance—a public-private partnership that subsidizes immunization in low-income countries. The United States and Russia, however, chose not to participate.
This snub by the world's remaining superpower and one of its principal challengers worried many observers. "I am concerned about what I call vaccine nationalism," CEPI executive director Richard Hatchett told the Los Angeles Times. "That's the tension between obligations elected leaders will feel to protect the lives of their citizens" versus the imperative for global sharing.
Some signs point to a possible rerun of the hoarding that accompanied the 2009 H1N1 influenza pandemic, when wealthy nations bought up virtually all vaccine supplies—denying them to poorer countries, and sometimes to one another. Operation Warp Speed has declared an "America First" policy for any vaccine arising from its efforts. Pharma giant Sanofi recently suggested that it would take a similar approach, since the U.S. was first to fund the company's COVID-19 research. (Sanofi's CEO backtracked after officials in France, where the firm is headquartered, protested.) The Oxford group, which is partnering with British-based drug maker AstraZeneca, intends to prioritize Great Britain.
Yet momentum is building for more generous strategies as well. In May, over 100 current and former world leaders, along with prominent economists and public health experts, issued an open letter calling for a "people's vaccine" for COVID-19, which would be patent-free, distributed globally, and available to all countries free of charge. At the WHO's annual World Health Assembly, all 194 member states accepted a resolution urging that vaccines for the disease be made available as a "global public good"—though the U.S. dissociated itself from a clause proposing a patent pool to keep costs down, which it argued might disincentivize "innovators who will be essential to the solutions the whole world needs."
Gavi, for its part, plans to launch a mechanism designed to encourage those innovators while promoting accessibility: an advance market commitment, in which countries pledge to purchase a vaccine, with no money down. Future contributions will be based on the value of the product to their health systems and their ability to pay.
"It's essential to realize that a threat anywhere is a threat everywhere."
A few private-sector players are stepping up, too. U.S.-based Johnson & Johnson, which has received nearly half a billion dollars from the federal government for COVID-19 vaccine research, has promised to provide up to 900 million doses on a not-for-profit basis, if its trials pan out. Other companies have agreed to produce vaccines on a "cost-plus" basis, with a smaller-than-usual profit margin.
How Sharing Can Pay Off
No one knows how all this will work out if and when a vaccine becomes available. (Another wild card: Trump has announced that he is cutting U.S. ties to the WHO over its alleged favoritism toward China, which could hobble the agency's ability to coordinate distribution -- though uncertainty remains about the process of withdrawal and reversing course may still be possible.) To public health experts, however, it's clear that ensuring accessibility is not just a matter of altruism.
"A historic example is smallpox," Rebecca Weintraub observes. "When it kept getting reintroduced into high-income countries from low-income countries, the rich countries realized it was worth investing in the vaccine for countries that couldn't afford it." After a two-decade campaign led by the WHO, the last case of this ancient scourge was diagnosed in 1977.
Conversely, vaccine nationalism doesn't just hurt poor countries. During the H1N1 pandemic, which killed an estimated 284,000 people worldwide, production problems led to shortages in the United States. But Australia stopped a domestic manufacturer from exporting doses to the U.S until all Aussies had been immunized.
Such considerations, Weintraub believes, might help convince even the most reluctant rich-country leaders that an accessible vaccine—if deployed in an epidemiologically targeted way—would serve both the greater good and the national interest. "I suspect the pressures put on our politicians to act globally will be significant," she says.
Other analysts share her guarded optimism. Kelly Moore, who teaches health policy at Vanderbilt University Medical Center, oversaw Tennessee's immunization programs for more than a decade, and later became a member of the Sabin-Aspen Vaccine Science & Policy Group—a panel of international experts that in 2019 released a report titled "Accelerating the Development of a Universal Influenza Vaccine." The 117-page document provided a road map toward a long-sought goal: creating a flu shot that doesn't need to be reformulated each year to target changing viral strains.
"One lesson we learned was that it's crucial to deploy financial resources in a systematic way to support coordination among laboratories that would typically be competitors," Moore says. And that, she adds, is happening with COVID-19, despite nationalist frictions: scientists from Sanofi joining forces with those at rival GSK; researchers at other companies allying with teams at government laboratories; university labs worldwide sharing data across borders. "I have been greatly encouraged to see the amount of global collaboration involved in this enterprise. Partners are working together who would normally never be partners."
For Moore, whose 77-year-old mother survived a bout with the disease, the current pandemic has hit close to home. "It's essential to realize that a threat anywhere is a threat everywhere," she says. "Morally and ethically, we have a tremendous obligation to ensure that the most vulnerable have access to an affordable vaccine, irrespective of where they live."
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online. For this reprinting of the article, we have updated the latest statistics on COVID-19 and related global news.]
CORRECTION: A sentence about DNA vaccines incorrectly stated that they require cold storage, like RNA vaccines. The error has been fixed.