As the potential threat of COVID-19 became clear by early 2020, teams across Pfizer sprang into action. Together, they worked to better understand the novel virus. Hospitals were filling, and no one was sure how best to treat the people who were sick. While some infected people seemed to recover quickly, others were dying.
We had started to think about how best we might be able to help address the pandemic, recalls Annaliesa Anderson, who is Senior Vice President and Chief Scientific Officer Bacterial Vaccines and Hospital at Pfizer. And the first, obviously was the vaccine. But the second was to be able to stop people from getting so sick that they had to go to a hospital.
At that time, Pfizer had a relatively small team dedicated to supporting the development of antibacterial therapeutics within the companys Hospital portfolio.1 But several long-time colleagues had worked on prior in-house discovery and development programs focused on viruses such as HIV, Hepatitis C, Rhinovirus, and SARS-CoV-1a virus that, in 2003, was spreading rapidly in Asia.2
One of those scientists is Jennifer Hammond, Vice President, Global Product Development at Pfizer. Hammond recalled pre-clinical work conducted within the Antiviral Discovery Group in 2003 on a SARS-CoV-1 main protease inhibitor, a small molecule which works by inhibiting viruses from making copies of themselves.2
While the SARS outbreak of 2003 resolved before the SARS-CoV-1 main protease inhibitor could be tested in humans,2 the similarity between the viruses causing both diseases suggested it could be a good place to start new research and development efforts. And data generated within Pfizer, as well as the broader scientific community, quickly emerged that confirmed the attractiveness of the main protease as a potential antiviral target.2
In parallel, other members from the team, together with colleagues from across Pfizer, were following the emerging data on the virus and exploring ideas to design a novel therapeutic agent. Within a week, this work came together, and a team was formed to explore the legacy compound, while another was tasked to design a novel, oral therapeutic agent.2
Over the next 24 months, more than 2,000 people came together from across the entire Pfizer organization to share their strengths and expertise to work toward the development of a therapeutic. The collective included experts in virology, oral small molecule design, synthesis, pharmacology, formulation, scale-up, clinical development, and more.3 All of this work began at a frightening time, when people around the world who were able to transition their work, schooling, and personal lives to be largely at home.
In order to be respectful of colleagues' new obligations at home, we actually asked for volunteers who could come on site and help work on this program synthesizing novel molecules, says Charlotte Allerton, Pfizers Head of Medicine Design. We had more volunteers than we actually needed for the program. And they were exceptional. Around the clock, they worked different shifts, juggling some of these challenges at home as well as really moving the program forward.
By March, Pfizer scientists had confirmed that the protease inhibitors from the original SARS program also blocked the SARS-CoV-2 main protease, meaning they had the potential to be used for treating COVID-19.3 However, because these inhibitors were only suited to be given intravenously, they were likely only going to be useful for treating patients who were ill enough to be in the hospital. To potentially benefit the most people and prevent them from going to the hospital, the team wanted to develop a novel oral treatment.3 We decided that we needed to design and develop a novel medicine that could be taken as a pill soon after infection to hopefully help prevent progression to severe disease, says Anderson.
Introducing a new drug (from discovery to approval) in the U.S. takes an average of 12 years.4 As COVID-19 surged around the world, the clock was ticking. The discovery team moved urgently, using structure-based design and state-of-the-art computational and synthetic technologies to identify a highly promising molecule to move into the clinic. With encouraging preclinical data in hand, they started to scale up activities and toxicology studies to enable the start of a Phase 1 study, just 12 months after the program had launched.1
In order to work quickly while still making safety the top priority, the team conducted some of the processes in parallel instead of taking a traditional stepwise approach, where one set of experiments is completed before the next one begins.1 What that meant to Pfizer was making an enormous financial investment in this treatmentincluding designing clinical trials in parallel, as well as making the medicine and packaging so it was ready to be sent immediately if the clinical trials were successfulwhile still not knowing whether it would be authorized or approved.1
Arthur Bergman, who is Group Head of Clinical Pharmacology in Pfizers Anti-Infectives Early Clinical Development, says that, in order to expedite the process, they designed a clinical study protocol that could be flexible and amended as needed along the way. That was valuable when it came to figuring out dosage, for example. He says that going into the Phase 1 part of the trialwhen theyre testing for safety, dosage, and potential side effects in healthy volunteersthe team wanted to safely maximize the concentration of the medicine in the body to be confident of achieving efficacy and minimizing resistance mutations. So they evaluated the molecule alone and co-administered with a pharmacokinetic booster, which helps the compound stay in the body longer, allowing for higher concentrations.5
Bergman says the U.S. Food and Drug Administration (FDA) and other regulatory agencies were critical in the effort to keep up this fast pace. Tasks that might traditionally take regulators a monthlike protocol reviewwere prioritized by the agencies and completed in a matter of days. And in many cases, the FDA would supply early feedback to help move things along quickly.2
In order to save time, another Pfizer team used technology to model and simulate clinical trial outcomes, in place of a traditional Phase 2 trial.2They did that using something called a viral kinetics model, which simulates virus replication in humans and also simulates the way the drug would inhibit that replication in people with COVID-19.2 That modeling data, along with the data from the trial that used healthy volunteers, informed the dose that would be focused on in the subsequent Phase 2/3 studies.2
With safety always a paramount priority, Pfizer enrolled an initial cohort of just 60 COVID-19-positive patients, who were at increased risk of progressing to severe disease, in the first of these studies (called a pivotal trial). All had experienced symptoms for no more than five days.2 Shortly thereafter, an external safety committee consisting of experts in critical care, infectious disease, cardiology, and other therapeutic areas, reviewed the data from that cohort for any potential health concerns.2 When that panel reported back no concerns, a flurry of activities began to launch the trial on a broader scale.
All told, 2,246 people participated in the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial; 41% came from the US and 59% came from around the world, with representation in South Africa, Western Europe, Eastern Europe, Thailand, Malaysia, Japan, Argentina, Mexico, and beyond.6The results were striking: in non-hospitalized adults with COVID-19 and at least one risk factor for progression to severe disease, the oral therapy was found to reduce the risk of hospitalization or death by 89% compared to a placebo when treated within three days of symptom onset.6
Bergman gets emotional when he reflects on the moment he learned the results. It still brings a tear to my eye today, thinking about how all the hard work from this team came together to create something with such potential to impact patients' lives, he says. You know, thats something that I'll never forget.
In December of 2021, the FDA granted emergency use authorization for the treatment of COVID-19 patients at high risk of progressing to severe diseasethe first oral treatment to be authorized to fight COVID-19. It was an exhilarating experience to be part of something that has such important potential for mankind, says Anderson.
But everyone who contributed to the endeavor knows the work isnt done yet. COVID-19 is still here, after all. Rhonda Cardin, Ph.D., who is Executive Director, Anti-Infectives at Pfizer, says scientists are continuing to watch the virus as it evolves. At our Pearl River, NY site, for example, we are monitoring the development of emerging variants in the GISAID (Global Initiative on Sharing Avian Influenza Data) database, which tracks virus sequences from around the world, she says. And were not only tracking the variants; were actively testing them against nirmatrelvir to understand whether our oral treatment will be able to treat the emerging variants.
For now, theyre cautiously optimistic. Hammond says that even as the virus mutates, research is finding that the protease inhibitor still seems to interfere with the ability of the virus to replicate, in part due to its ability to bind tightly to its target.2 But, as always, theyll be keeping a careful eye out for any changes and responding to them accordingly. We are definitely remaining vigilant because viruses surprise us all the time, she says.
Pfizer's oral treatment has not been approved, but has been authorized for emergency use by the FDA to treat mild-to-moderate COVID-19 in patients 12 and older, weighing at least 40 kg, with positive results of SARS-CoV-2 viral testing, who are at high risk for progression to severe COVID-19, including hospitalization and death. Authorized only for the duration of the declaration that circumstances exist justifying the authorization unless the declaration is terminated or authorization revoked sooner. See EUA Fact Sheet: www.COVID19oralRx.com
References:
Good morning, Mission, and welcome to Virus Village, your (somewhat regular) Covid-19 data dump.
Hospitalizations, positivity rates, R Number models and wastewater monitoring are all up, while recorded infections remain flat.
Omicron sub-variants BA.4 and BA.5 are now taking over as the dominant strains in the world and will soon be dominant in the U.S. These variants are the most contagious yet. The virulence is open to question, but a rise in hospitalizations around the world, particularly in heavily vaxxed Portugal is not a good sign.
Here is a summary of the new variants.
What steps is San Franciscos Department of Public Health taking to mitigate transmission or warn of the dangers posed by the new variants?
Yesterday a subcommittee of the FDA recommended another booster for the fall which has been reconfigured to take into account omicron. But it was designed for omicron .1, not omicron .4 or .5. The data on the effectiveness of the vaccine is very limited, giving rise to a variety of interpretations.
Here are pros and cons for the new booster.
A universal corona virus vaccine is now being tested. This seems better than chasing after variants that keep changing.
High community spread undermines the effectiveness of individual responsibility and the use limited clinical tools. Understanding the infectivity of the airborne virus would seem logical, as would an emphasis on ventilation.
High community spread and re-infection increase the likelihood of long covid, says the World Health Organization. Heres an interview with UCSFs Dr. Lekshmi Santhosh on what we know and dont know about long covid.
What are the covid protocols in hospitals? Do they segregate covid patients from others? Do hospital workers wear N95s? Do they clean the air? How? And how often? Here is a summary on actions taken by academic hospitals around the country. There are no standards, and the diversity of practice is somewhat shocking. But not surprising.
Whats happening in San Francisco hospitals? Who knows? Our local celebrity experts prefer to discuss individual risk calculation rather than what their hospitals are doing to protect workers and patients.
Determined inaction by government officials at all levels has left us vulnerable to new variants and repeated surges. But why would anyone deliberately degrade community hubs, one of the most effective and hopeful programs developed in the City? As Ed Yong points out, community work has been foundational in fighting any pandemic.
Over 4 million (!!!) papers, studies and preprints have come out on covid, and we still know so little.
Scroll down for todays covid numbers.
Over the past week, hospitalizations jumped 33 percent (representing 27 more patients). On June 25, DPH reports there were 108 covid hospitalizations,or about12.4 covid hospitalizations per 100,000 residents (based on an 874,000 population). ICU patients had climbed to 22, but have fallen back to 15. The California Department of Public Health currently reports 115 covid patients in SF hospitals with 23 patients in ICU.
The latest report from the federal Department of Health and Human Services shows Zuckerberg San Francisco General Hospital with 12 covid patients and 8 ICU beds available, while across the Mission, CPMC had 8 covid patients and 4 ICU beds available. Of 106 reported covid patients in the City,52 were at either SFGH or UCSF, with at least 72 ICU beds available among reporting hospitals (which does not include the Veterans Administration or Laguna Honda). The California DPH currently reports 104 ICU beds available in San Francisco.
Between April 25 and June 24, DPH recorded 1,389 new infections among Mission residents (an increase of 5.8 percent from last week) or 250 new infections per 10,000 residents. During that period, Mission Bay continued with the highest rate at 432 new infections per 10,000 residents. Although Mission Bay was the only neighborhood with a rate above 400, 14 others had rates above 300 per 10,000 residents, with 9 in the east and southeast sectors of the City. In a surprise, Seacliff posted a rate of 327 per 100,000 residents (perhaps the City will pay more attention to transmission now).
DPH reports on June 21, the 7-day average of daily new infections recorded in the City rose to 422 or approximately 45.7 new infections per 100,000 residents (based on an 874,000 population), basically flat since last week. According to DPH, the 7-day average infection rate among vaccinated residents was 48.2 per 100,000 fully vaccinated residents and 94.8 per 100,000 unvaccinated residents. It is unclear whether fully vaccinated means 2, 3 or 4 doses. According to the New York Times, the 7-day average number on June 21 was 465. The latest report from the Times says the 7-day average on June 28 was 492, a 1 percent decrease over the past two weeks. As noted above, wastewater monitoring shows a substantial rise in the southeast sewers. This report comes from the Stanford model. The state is still reporting staffing problems.
So far in June, Asians recorded 3,279 new infections or 31.1 percent of the months cases; Whites 2,388 infections or 22.6 percent; Latinxs 1,333 infections or 12.6 percent; Blacks 484 infections or 4.6 percent; Multi-racials 72 infections or 0.7 percent; Pacific Islanders 54 infections or 0.5 percent; and Native Americans had 23 recorded infections in May or 0.2 percent of the June totals so far.
On June 21, the 7-day rolling Citywide average positivity rate rose 10.9 percent during the past week to 14.3 percent, while average daily testing dropped approximately 7.4 percent. Over the past two months, the Mission has had a positivity rate of 10.8 percent.
Vaccination rates in SF show virtually no change from last week.
For information on where to get vaccinated in and around the Mission, visit ourVaccination Page.
Nine new covid-related deaths, with 7 more in June, have been reported, bringing the total since the beginning of the year to 215. DPH wont say how many were vaccinated. Nor does it provide information on the race, ethnicity or socio-economic status of those who have recently died. According to DPH COVID-19 deaths are suspected to be associated with COVID-19. This means COVID-19 is listed as a cause of death or significant condition on the death certificate. Using a phrase like suspected to be associated with indicates the difficulty in determining a covid death. The fog gets denser as DPH reports, incredibly as it has for months, only 21 of the deaths are known to have had no underlying conditions, or comorbidities. DPH only supplies cumulative demographic numbers on deaths.
The lack of reliable infection number data makes R Number estimates very uncertain. Covid R Estimation on June 24 estimated the San Francisco R Number at 1.21 while its estimate for the California R Number on June 27 was 1.26. The ensemble, as of June 26, estimated the San Francisco R Number at .97 and its California R Number at .97. Note: All but one model in the ensemble show SF under 1.
So far in June, DPH reports 56 new infections and 0 new deaths in nursing homes (skilled nursing facilities), while in SROs (Single Room Occupancy hotels), DPH reports 40 new infections and 1 new death.
Dr. Gregory Poland, an infectious disease physician at Mayo Clinic in Rochester, told 5 EYEWITNESS NEWS the original vaccines against the COVID-19 virus did a terrific job keeping people out of the hospital and preventing death, but he said moving forward better vaccines need to be developed.
The current vaccines offer only mild benefit, in terms of infection, against those new variants, said Poland. So, the idea is, and both Moderna and Pfizer both plan no doing this, to devise vaccines that cover the Omicron variant.
Poland told 5 EYEWITNESS NEWS the goal is to possibly have an updated COVID vaccine by early fall by using part of the original vaccine and the vaccine that was used during the Omicron surge.
But, Poland said the ultimate goal is to develop a so-called Pan-Corona Vaccine which would offer better protection against all of the variants that have emerged with the virus.
The idea that we, and others are working on, is a Pan-Corona virus vaccine. Or, if you will, a universal Corona virus vaccine, said Poland. Thats still a ways off, but thats the goal.
Dr. Peter Bornstein, with St. Paul Infectious Disease Associates, told 5 EYEWITNESS NEWS he agrees with the push by the Food and Drug Administration to come up with a more effective vaccine.
We definitely need better vaccines. How much the virus itself will keep mutating, and have immunological escape from the vaccines, we just dont know yet, said Bornstein.
The FDA met Tuesday to discuss the future of new COVID vaccines, but did not yet offer any recommendations.
A national nonprofit wants to better understand how Filipino communities across the country feel about COVID-19 vaccines.
Researchers from the Filipino Young Leaders Program, which seeks to advance Filipino voices through advocacy, said its important to have disaggregated data to show the pandemics impact on Filipino communities.
To have this type of data it helps not only with the resources, but it also helps in understanding the health information, said Chachie Abara, who is helping survey researchers with local efforts. It really helps highlight a lot of information in terms of how we can provide the support in the continental U.S. and here in Hawaii.
Abara, who moved from the Philippines to Hawaii as a child, pointed out that its also key to understand why some people are hesitant to get vaccinated.
In Hawaii, Filipinos have been hit hard by the pandemic.
About 24% of those who died from COVID-19 identified as Filipino, according to the state Department of Health. That represents the highest share among all ethnic groups.
Also, about 17% of people in Hawaii who tested positive for COVID-19 are Filipino, according to the state Health Department.
The 20-minute survey is conducted online and on the phone in English and Tagalog. It is open to Filipino Americans who are at least 18 years old, regardless of vaccination status.
For more information and to participate in the survey, click here.
A U.S. Army combat medic draws the COVID-19 vaccine into a syringe. (Aaron Rodriguez/National Guard)
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NASHVILLE, Tenn. (Tribune News Service) A group ofTennessee National Guardmembers, who face being forced out of the service by theU.S. Department of Defenseon Thursday over their refusal to get mandated COVID-19 vaccines, along with their supporters pleaded publicly with Gov.Bill Leeon Wednesday to take actions, including suing the federal government if necessary, to prevent their dismissal.
OnJune 30, hundreds of yourTennessee National Guardsoldiers under an illegal, improper order by the Biden administrationsDepartment of Defensein defiance of natural law and the United States Constitution are scheduled to be dismissed from service due to refusal to accept a COVID-19 vaccination, read a petition presented to the stateCapitoloffice of Lee by several dozen Guard members, their families and friends.
It is your duty before God and the citizens of the great state of Tennessee, sir, to help these men and women. Please stop them from being fired, sir! the petition tells Lee, a Republican.
The governor was not in the office to accept the petition.
Ricky Shelton, aTennessee National Guardcaptain fromGrainger Countywho is a member of the230th Sustainment Brigadeout ofChattanooga, helped lead the effort. Several Republican lawmakers voiced support for the guard members as well.
Standing outside the governors office suite, Shelton told theChattanooga Times Free Presshe had been unsuccessfully trying to meet with Lee.
Theyve ignored and theyve ignored and diverted and tried to avoid whether its an event we invited them to or whatever it may be, said Shelton, who along with comrades and other supporters rallied earlier onLegislative Plazabefore the stateCapitol. So theyve avoided us like a plague.
He said he had been in back-and-forth conversations with Lee Chief of StaffJoseph Williamsto set up a meeting, but it had not come through by Wednesday.
Rep.Jerry Sexton, R-Bean Station, was among a group of Republican lawmakers joining the protesters onLegislative Plazafor their rally. He later accompanied them into theCapitolto Lees offices.
Were here to stand with theTennessee National Guardto support them and their effort to not take the vaccine and to encourage our governor and attorney general to do all that they can do, whatever they can to push back against this, Sexton told theTimes Free Press. They dont need to lose their jobs. And we dont need to lose them, you know, in our defense.
Lee CommunicationsDirectorLaine Arnoldlater issued a statement to theTimes Free Press.
The COVID-19 vaccine mandate is aDepartment of Defenserequirement, the statement said. But we have approved every personal and religious exemption brought forward by members of the Guard.
We have also advocated to theDoDthat personnel who sought an exemption should receive that same exemption federally, and we are awaiting their response. In the meantime, we have no plans to terminate or dishonorably discharge personnel.
Shelton said he personally objects to the COVID-19 vaccines because, he added, human tissue from aborted fetuses were used to develop or make the vaccines.
The groups requests to Lee include:
Publicly condemning firings ofTennessee National Guardmembers who are scheduled to be terminated due to their refusal of the COVID-19 vaccine. They also want Lee to do everything in your power to help those members.
Immediately orderTennessee National Guard Adjutant Generaland Maj.Gen. Jeff Holmesto halt the discharge of the men and women refusing the vaccinations.
Ask Tennessee Attorney GeneralHerb Slateryto file suit on behalf of theTennessee National Guardmembers and coordinate with other states attorneys general to file an emergency injunction against theDepartment of Defense, forcing them to reverse adverse actions against any National Guardsman for refusal to vaccinate.
We pray that you find it in your heart and your character to take action. Please join us in fighting for the men and women of theTennessee National Guard, the petition adds.
According to The Associated Press, up to 40,000Army National Guardsoldiers across the country or about 13% of the force have not yet taken the mandated COVID-19 vaccine, and as the deadline for shots looms, at least 14,000 of them have flatly refused and could be forced out of the service.
Guard leaders say states are doing all they can to encourage soldiers to get vaccinated by the time limit. And they said they will work with the roughly 7,000 who have sought exemptions, which are almost all for religious reasons.
You are their commander-in-chief, the petition says to Lee. We implore you to do everything within your power to fight for these dedicated men and women. To date, sir, you have been silent. We implore you to be silent no more.
Shelton told theTimes Free Pressthat after this now, honestly, I dont care what happens to me. Because this is more important because we were always taught to take an oath to defend our soldiers And if their health is being affected and nobodys stepping up for them, it is my duty to do that.
And I will walk through hell with a can of gasoline in each hand and back for my soldiers if I had to, Shelton added.
(c)2022 the Chattanooga Times/Free Press (Chattanooga, Tenn.)
Visit at www.timesfreepress.com
Distributed byTribune Content Agency, LLC.
DHHR has confirmed the deaths of a 71-year old male from Pleasants County, a 94-year old female from Wood County, an 82-year old female from Cabell County, an 88-year old female from Pleasants County, and a 96-year old female from Ohio County.
We offer our deepest sympathies as the families and our state grieve more losses due to COVID-19, said Bill J. Crouch, DHHR Cabinet Secretary. Each life lost is one too many, and we must do everything we can to stop the pandemic including getting vaccinated and boosted.
CURRENT ACTIVE CASES PER COUNTY: Barbour (11), Berkeley (125), Boone (46), Braxton (24), Brooke (15), Cabell (108), Calhoun (7), Clay (9), Doddridge (3), Fayette (52), Gilmer (4), Grant (13), Greenbrier (55), Hampshire (25), Hancock (31), Hardy (11), Harrison (89), Jackson (22), Jefferson (63), Kanawha (239), Lewis (18), Lincoln (19), Logan (37), Marion (83), Marshall (29), Mason (21), McDowell (31), Mercer (76), Mineral (32), Mingo (24), Monongalia (114), Monroe (19), Morgan (14), Nicholas (31), Ohio (41), Pendleton (2), Pleasants (13), Pocahontas (4), Preston (26), Putnam (90), Raleigh (95), Randolph (18), Ritchie (9), Roane (22), Summers (18), Taylor (27), Tucker (8), Tyler (4), Upshur (41), Wayne (28), Webster (13), Wetzel (15), Wirt (3), Wood (97), Wyoming (31). To find the cumulative cases per county, please visit coronavirus.wv.gov and look on the Cumulative Summary tab which is sortable by county.
West Virginians ages 6 months and older are recommended to get vaccinated against the virus that causes COVID-19. Those 5 years and older should receive a booster shot when due. Second booster shots for those age 50 and over who are 4 months or greater from their first booster are recommended, as well as for younger individuals over 12 years old with serious and chronic health conditions that lead to being considered moderately to severely immunocompromised.
Visit the WV COVID-19 Vaccination Due Date Calculator, a free, online tool that helps individuals figure out when they may be due for a COVID-19 shot, making it easier to stay up-to-date on COVID-19 vaccination. To learn more about COVID-19 vaccines, or to find a vaccine site near you, visit vaccinate.wv.gov or call 1-833-734-0965.
To locate COVID-19 testing near you, please visit https://dhhr.wv.gov/COVID-19/pages/testing.aspx.
On a cold, damp Monday just over a year into the pandemic, Jacob Hopkins tilted his head back in a London hospital and did something no other human had ever done before: He allowed five doctors in full hazmat garb to dribble into his nostrils a precisely calibrated suspension of the coronavirus that causes COVID-19.
Hopkins would go on to become one of the more than 546 million people across the globe to be infected with the virus known to scientists as SARS-CoV-2.
He did it for science.
Hopkins was the first of 36 healthy young Britons to participate in a human challenge study of the most consequential virus on the planet. The experiment was widely accepted in the United Kingdom as an efficient way to gain insights into how, where and for how long the virus establishes itself in people.
Knowing the minute details of a coronavirus infection is critical to vaccine and drug designers, to public health officials, and to those caring for patients. Many of those details remained elusive until the studys findings were published this spring.
Jacob Hopkins rests his arm near vials of blood that were drawn to study what the coronavirus does inside the body.
(Jacob Hopkins)
Hopkins had only a fuzzy sense of how his act might help others. As a teenager, he had responded to a cousins leukemia by signing up with a stem cell registry, and ended up donating bone marrow. This time, he hoped his participation might speed the development or testing of vaccines for low-income countries.
I would have been devastated if I couldnt take part, he said.
In the United States, deliberately infecting humans with the coronavirus was so controversial that American officials declared it a last resort. They argued that scientists could find ways to unlock the virus secrets without exposing volunteers to even a tiny risk of death.
Human challenge studies were Plan D, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who contemplated them only as a way to put a new vaccine through its paces.
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Experiments that intentionally expose healthy volunteers to serious harm pose deep quandaries. Thats especially true when too little is known about a virus to predict its impact, and when effective treatments arent available.
But in the next pandemic, or even later in this one, some U.S. scientists say they may rethink their resistance.
We can learn things more quickly by doing challenge studies, said Dr. Stanley Plotkin, a University of Pennsylvania vaccinologist who was a leading voice in calling for such research.
When an infectious disease is spreading out of control, saving time may be worth the risk, said Arthur L. Caplan, a bioethicist at New York University.
If volunteers were willing to be infected, you could prevent potentially millions of deaths, he said.
::
Jacob Hopkins took this selfie while he was participating in a human challenge trial to help scientists learn more about SARS-CoV-2.
(Jacob Hopkins)
Jacob Hopkins path to becoming a human guinea pig wasnt particularly fraught. He had always been fit, he said, and volunteering felt like something I could do.
Hopkins was a 22-year-old history student at Newcastle University when Britain imposed the first of several strict lockdowns. He went home to live with his parents in Birmingham after his school closed.
In the final months of 2020, Hopkins was working in a grocery store and scrolling through his social media feed when he saw an ad with pictures showing attractive people masked and socially distanced, but otherwise equipped with the usual accoutrements of young adulthood backpacks, schoolbooks and earbuds.
Help us fight COVID-19, said the advertisement. Stripped across the bottom, in fine print, was a disclaimer: You may suffer COVID-19 symptoms if you take part.
It seemed like a way to help the world get back to normal faster. Hopkins first love, backpacking abroad, was not an option. Nor was socializing at home. His studies in Cold War history had been put on hold. But the prospect of playing some small role in this historical moment gave him a sense of mission.
In fact, hands shot up across the world. Hopkins was one of nearly 37,000 people who expressed initial interest in participating in the study. Researchers screened 6,135 by phone, winnowing the unresponsive, the unsure and those who were too old or too sick. With 187 potential candidates left, they pruned people whod become infected, lost interest or had gained access to vaccine. Thirty-six, including Hopkins, were deemed healthy, stable, ready to go.
His parents were definitely not happy, Hopkins said. But he was determined to see it through. While his countrymen were letting down their guard after a third round of lockdowns, Hopkins double- and triple-masked when in public. If he got infected before the study began, hed be disqualified
I never wanted to get COVID, Hopkins said, and then quickly corrected himself. Well, I did want COVID, but I wanted it at the right time.
::
In the U.S., scientists at the National Institutes of Health took a step toward launching a U.S. human challenge trial early in the pandemic. The government ordered up SARS-CoV-2 viral samples that could be used to deliver precise, genetically identical doses to human subjects.
But that, Fauci told CNN at the time, was an absolutely far-out contingency.
He stands by that decision nearly two years later. Even if researchers had an urgent need to test a new vaccine, they could do so without infecting volunteers because the coronavirus is readily available in the world at large, he said in an interview.
Plotkin was among the scientists who lobbied the NIH to conduct a human challenge trial. He said officials were concerned that a volunteer would be harmed and that if that happened, the reputation of the NIH would be harmed.
The British, by contrast, were interested right from the beginning, he said.
A daytime view of London from Jacob Hopkins hospital room.
(Jacob Hopkins)
The United Kingdom was uniquely positioned to move ahead quickly with a human challenge study. The National Health Service provides care for all Britons, so participants medical and mental health histories are readily available. Its universal healthcare system also means that research subjects would never be refused follow-up care if something went awry. (Neither is the case in the U.S.)
British researchers had a long tradition of studying infectious diseases including influenza, common cold viruses and malaria using controlled human infection models. The practice came of age in 1946, when Britain repurposed a wartime hospital in Salisbury as a Common Cold Research Unit.
Compensation was the principal inducement for participation, and it remained that way for decades. Healthy people with time on their hands could spend a couple of weeks in what was sometimes billed as Flu Camp. Theyd depart well-fed and rested, with some cash in their pockets.
With the COVID-19 study, it was clear that volunteers motives were overwhelmingly altruistic, said Carol Dalton, a spokeswoman for hVIVO, the clinical research company that carried out the COVID-19 study with scientists from Imperial College London. Participants earned 4,565 British pounds (about $5,500) for a 17-day hospital stay and several follow-up visits, though the pay was not a prominent feature of the hVIVO advertisements.
Separately, more than 38,000 people reached out to 1DaySooner, an online clearinghouse for people willing to participate in human challenge studies. Hopkins signed up on that website, as well as on the studys official enrollment site.
There was no precedent for so many volunteers asking scientists to put their own health at risk in such a trial, said Abie Rohrig, a student of bioethics at Swarthmore College who helped set up 1DaySooner.
::
One of Jacob Hopkins meals during his hospital stay.
(Jacob Hopkins)
Hopkins took that risk in stride. He said he understood he was taking a chance, but he was more concerned about developing long COVID, an array of lingering post-infective symptoms, than he was about catching COVID-19 itself.
As he anticipated spending weeks holed up in St. Marys Hospital in Londons Paddington quarter, he had high hopes for using his time well. He thought he might learn British sign language online and stream some movies for fun.
But the schedule didnt leave much time. Participants started each day in front of a laptop, churning through a battery of odious cognitive tests. There was also a daily scratch-and-sniff smell test and the hour he spent with his face buried in a plastic mask that measured his respiratory output. Research staff, often unrecognizable under layers of protection, were in and out of his room all day taking vital signs and drawing blood.
Meals were tasty but spartan. A bag of crisps showed up on his tray once or twice, prompting great excitement.
Strictly isolated in his hospital room, he gazed out the window at the London Eye, the citys famous Ferris wheel, and lost himself in the reassuring nostalgia of classic video games like The Sims and Ratchet & Clank.
On two occasions, Hopkins was bundled into his own hazmat suit and wheeled to a CT scanner. Those days were rare treats, when we were seeing something other than the four walls of a very sterile room, he said.
Getting the study underway took a year of debate and preparation. By the time British scientists deliberately infected Hopkins on March 2, 2021, several COVID-19 vaccines were beginning to go into arms across the United Kingdom. It was a milestone but it threatened to derail the human challenge study, which had been intended to help with vaccine development.
We had to completely rethink what this study was for, said Dr. Christopher Chiu, an immunologist and infectious disease specialist who led the team from Imperial College London. With so much still unknown about the virus, there was still a public health need, Chiu said. And researchers testing antiviral medications would still need to know how much virus it took to seed an infection.
So the aim was recast. The trial would identify the exact dose at which an exposure to SARS-CoV-2 virus would infect half of healthy young people. And it would track the coronavirus behavior and its interaction with its hosts across the length of infection.
The studys findings were reported this spring in the journal Nature Medicine.
Among its insights:
Even at the lowest concentration measurable in a lab, SARS-CoV-2 virus established a beachhead in the throats of just over half of the young, healthy subjects within two days.
The viral loads in their noses reached peak concentration an average of five days after exposure.
Whether or not subjects developed COVID-19 symptoms, they were capable of infecting others for an average of five more days.
None of the infected became seriously ill, but 83% lost their sense of taste or smell; in most cases, it returned slowly over three months. None experienced lung damage.
The findings made powerfully clear that young people have been potent drivers of pandemic spread. Further analysis of the findings is expected to yield insights into how the immune system resists infection, and why some people become infected while others do not.
So were these insights worth the risk taken by Hopkins and his fellow volunteers?
Chiu, the senior author of the paper detailing the studys findings, thinks so.
Theres unique strength to the findings from this kind of study, Chiu said. You capture every part of infection from the point of exposure to the end.
In the U.S., Caplan said he was frustrated that so much of the medical establishment was wary of allowing healthy Americans to be deliberately infected, when doing so could have yielded lifesaving insights.
People who sign up for such experiments must never be compelled to do so, Caplan said, nor induced with extravagant rewards. But people in many walks of life from test pilots and deep-sea divers to virologists who collect bat guano from caves take risks for science, he said. Every day, regular folks volunteer for early clinical trials of experimental drugs, where the correct dose is unknown and its safety is still very much in question.
Its a noble thing to do, he said, adding that many Americans wanted to do it: We knew because wed been asked.
::
This hospital room was Jacob Hopkins home for 17 days while he weathered a case of COVID-19 for the sake of science.
(Jacob Hopkins)
Hopkins said hed do it again, in a heartbeat.
Though the virus plunged him into a two-day ordeal of feeling rubbish, it was an enormous relief to realize he had become infected. After the tests he endured to get into the study, and after fending off so many COVID-19 surges, he finally had something to offer. He high-fived one of the doctors who dribbled virus down his nose.
During his entire bout, researchers tracked hour by hour the rise and fall of his vital signs, his viral loads, his altered cognitive state and his immune systems strenuous effort to clear the virus.
Column One
A showcase for compelling storytelling from the Los Angeles Times.
When at last it did after 17 days, Hopkins received a check for 1,535 British pounds (nearly $1,900); the remainder was held in reserve pending follow-up visits.
All I did was sat in a room, said Hopkins, who now counsels low-income Britons on how to secure access to nutritious food. But I was so proud and happy to be a part of this. I was really part of something special.
On his last day at the hospital, as Hopkins slung his rucksack over his shoulder and marched toward the exit, the men and women who had taken his vital signs, delivered his meals and monitored his progress showed up to applaud him.
It was a heros farewell.
Cracking a window can help reduce the risk of indoor COVID transmission. Tanishka R./NPR hide caption
Cracking a window can help reduce the risk of indoor COVID transmission.
We regularly answer frequently asked questions about life during the coronavirus crisis. If you have a question you'd like us to consider for a future post, email us at goatsandsoda@npr.org with the subject line: "Weekly Coronavirus Questions." See an archive of our FAQs here.
Over the past two years, we've all had a crash course in understanding how to prevent respiratory infections.
And we've learned that clean air via ventilation (i.e. fresh air flow via open windows and doors) and filtration (removing particles from the air with a filtering device) is really important for preventing COVID and other respiratory illnesses. It's something many experts knew all along. Now the public is catching on.
"Most of the air that we breathe in our lifetimes, we breathe indoors," says Richard Corsi, dean of the University of California Davis College of Engineering. And virus particles can linger in the air of unventilated places, increasing chances of getting sick.
Of course, those particles are not visible. "If people could see COVID in the air, it would make a lot more sense that what you need to do is clean the air in your house, exchange the air out, get fresh air in, improve ventilation so that you don't have a lot of air hanging around where other people can breathe it in and get infected," says Abraar Karan, an infectious disease physician at Stanford University.
So what can you do, as an individual at home, work, school, the gym to make the air cleaner and safer?
That's what we asked three experts.
What's the most basic way I can improve ventilation?
"Just getting more air flow into the house itself" helps, Karan says.
Open windows if you can, says Linsey Marr, professor of civil and environmental engineering at Virginia Tech. "Especially if you can open them on opposite sides of the room, so you get some cross-ventilation air coming in one and going out the other."
Even if you can't open all of the windows or can't open them all of the way, cracking windows a little bit is still very helpful. "They don't have to be wide open," Marr says.
Opening doors in shops and gyms also helps.
Marr worked with the owner of her local gym to improve ventilation early in the pandemic. The gym didn't have central air conditioning, so it couldn't rely on filtration. The easiest option was to open the doors. "I estimated how much benefit we would get from opening the doors and it was a ton, so we kept them open all winter," Marr says.
And there was no known transmission in the gym, says Marr, who advised the facility and kept track of COVID developments. Even when staff picked up the virus from other places, they don't seem to have passed it on at work, she says.
How can I improve my home filtration system?
If you have an HVAC system forced air heating/cooling/ventilation you can do two main things: run the fan more and upgrade the filter in order to catch more viral particles. Every HVAC system has replaceable filters that trap allergens and dust in the air and viral particles, too.
HVAC systems typically don't circulate air 24/7, only running part of the time when indoor temperatures drop or rise.
To make sure the air is getting filtered through the HVAC system, "if you can, run the fan continuously," Corsi says.
When the windows are open, you can also turn on other fans, like the bathroom and kitchen exhaust fans, to "help pull in that clean air from the outside and flush out the virus," Marr says. True, they can be noisy, but they can create some air flow by pulling the air up toward the ceiling and out of the room.
But when the windows are closed, most home HVAC systems simply recirculate the same indoor air, and the standard filters you use may not be effective at catching the tiny virus particles. So you can also look into replacing those filters with higher-quality options, like a filter with a minimum efficiency reporting value (MERV) of 13.
"If you can put a MERV-13 filter in your HVAC system and if the fan is recirculating continuously, then you're going to remove a lot of the aerosol particles," Corsi says.
The majority of school ventilation systems can also be upgraded to MERV-13 filters, he says.
But, he cautions, not all systems can handle the more effective filters, so it's a good idea to have an HVAC specialist inspect yours. You don't want your whole system to break down because it is too strained trying to pull air through incompatible filters.
HEPA is another kind of filter that is even more effective at removing viruses from the air, but most home HVACs don't work with HEPA filters. However, you can get a portable HEPA air purifier.
Can portable purifiers help?
"If it says HEPA, then it's going to filter out over 99% of the air that passes through it," Marr says. "In general, price goes with size in terms of how much air it moves through it." That means the bigger the unit, the more it costs.
It's important to find the right-sized unit to purify the air of a room in an hour or two. "There's a big difference between like a $50 one that can clean the air in a closet in a reasonable amount of time and a much bigger one that probably costs $200 or $300 and can clean the air in a bedroom in a reasonable amount of time," Marr says.
But, she says, there are cheaper options: for eaxmple, a do-it-yourself system involving a simple box fan a portable model that is typically square, has a propeller blade and can often fit in a window and MERV-13 filters. That "is actually more effective in many cases" than expensive HEPA units, says Marr.
Known as the Corsi-Rosenthal box after its creators, this DIY filter is easy and inexpensive to make: you create a square shape with four filters making up four sides and the fan, pointing up toward the ceiling, duct-taped on top. A piece of cardboard is taped to the bottom, and the homemade air purifier can be put anywhere a more expensive purifier might go.
Karan agreed. "The Corsi-Rosenthal box is basically a very low-cost way to get better ventilation."
Corsi also agreed and only partly because he was one of the inventors. When he first sketched out the idea early in the pandemic, he thought it might be a more cost-effective way to offer some air filtration. And it is the materials cost between $80 and $100.
"But I also didn't realize how incredibly effective it would be," Corsi says.
The boxes can be up to 2.5 times more effective than a $300 HEPA filtration unit, according to a study by other researchers.
No matter what portable filtration system you go with, make sure you position it carefully. Don't put the device in a corner, where it might just recirculate the same air. Keep your purifier a foot or so away from the wall for the same reason.
For larger rooms, two or more units can be a good idea, says Corsi, and you can put them across the room from each other so all the air in the room gets filtered well.
What about those little travel-size air filters? Any benefit?
You might have seen little HEPA purifiers about the size of a water bottle that you can stash in a purse or backpack. But do these small devices actually help?
"They should, and you'd want to direct the airflow," Marr says. "That can clean a small area of a small amount of air."
Just make sure you position the stream of clean air as close to your face as possible, setting it on the table or desk in front of you.
"If you're using them so that the air is right in front of you working at your desk and it's blowing the air up toward your face, it can reduce the concentrations of aerosols as you're breathing," Corsi says. "I wouldn't overemphasize their benefit, but there can be some benefit."
Such purifiers, which cost $30 to $50, can add another layer of protection while you're traveling, eating at restaurants or going to work or school.
Should I buy a CO2 monitor to check how good the ventilation is in different places I go?
"If you are a very cautious person, then that can be a good tool to help you gauge the risk in different spaces," Marr says.
CO2 monitors measure how much carbon dioxide is in the air. They can't tell how much COVID is in the air, but if there is a lot of CO2 in a space, then it's not well-ventilated.
If the CO2 readout is under 1,000, that's pretty good. Anything over 1,800 is a warning sign that a space is poorly ventilated. At high rates, you're breathing in a lot of "other people's exhaled breath like drinking backwash," Marr says a nice way of saying drinking other people's spit while sharing a drink.
But these are loose rules that depend on how big the space is, how many people are there, whether they are masked, and how many cases are circulating in the community.
"I'm not a big fan of using CO2 monitors for very specific analysis," Corsi says. "They're not exact." But, he says, they are very useful for telling you when air quality is very good or very poor.
Does improving ventilation mean I can skip wearing a mask?
Improving air quality means you're less likely to get sick, because there's less virus in the air. But it's not 100% effective.
The experts all agreed that wearing a mask is one of the most effective ways to reduce your chances of getting sick even further, or if you're sick passing the virus on.
That means you should continue to mask up in indoor public places when cases are high, as they are in the U.S. right now.
And if you're sick or someone in your household is, wearing a mask can keep the virus from transmitting even at home.
"If you have someone who is sick, then you want to try, if it's reasonable, to have them wear a mask because that will reduce the amount [of virus] that gets into the air in the first place," Marr says. And it's a good idea to mask up when you are around them to protect yourself.
If a family member gets sick, will good ventilation keep me from catching COVID?
Yes! It may take a little work, but it is possible to stop transmission in the home.
As an infectious disease doctor, Karan has seen many patients who got sick at home from other family members. "That's the one thing that we have a really hard time with right now," he said.
But "I know that there are ways you can make the home safer I've done it myself," Karan says.
All of the advice the experts offer here is especially important to keep cases from spreading at home: open windows, have a fan blowing air out the windows, wear masks as source control, improve air filtration.
In the sick person's room, try to keep the door closed and face a fan to blow out the window, so "what they're emitting into their room doesn't get back into the rest of the house underneath the door and that kind of thing," Corsi says. "That'll actually go a long way to helping others in the house not get infected."
Should I press for better air quality in public spaces?
Sometimes you will be in places where you can't control air quality, like at work, school, restaurants or businesses.
But it doesn't hurt to ask what improvements such places have made to air quality. If you're worried about your kid returning to school in the fall, for instance, you can talk to the teacher about opening windows or using a portable air filter.
"We need to be holding businesses and then the government responsible," Karan says, to make sure they upgrade ventilation and establish new indoor air quality standards.
"It's not just about COVID," he says. Cleaning the air can reduce other respiratory viruses, like the flu and RSV, as well as mold and allergens.
It's easy to want to give up on COVID precautions, thinking this is the best we can do. But "people need to hear that there is a way to solve this problem," Karan says.
"We're not going to eliminate COVID. But what we can do is we can reduce COVID transmission significantly."
His verdict: "Ventilation is the way forward."
Melody Schreiber (@m_scribe) is a journalist and the editor of What We Didn't Expect: Personal Stories About Premature Birth. c
GENEVA -- The number of new coronavirus cases rose by 18% in the last week, with more than 4.1 million cases reported globally, according to the World Health Organization.
The U.N. health agency said in its latest weekly report on the pandemic that the worldwide number of deaths remained relatively similar to the week before, at about 8,500. COVID-related deaths increased in three regions: the Middle East, Southeast Asia and the Americas.
The biggest weekly rise in new COVID-19 cases was seen in the Middle East, where they increased by 47%, according to the report released late Wednesday. Infections rose by about 32% in Europe and Southeast Asia, and by about 14% in the Americas, WHO said.
WHO Director-General Tedros Adhanom Ghebreyesus said cases were on the rise in 110 countries, mostly driven by the omicron variants BA.4 and BA.5.
This pandemic is changing, but it's not over, Tedros said this week during a press briefing. He said the ability to track COVID-19's genetic evolution was under threat as countries relaxed surveillance and genetic sequencing efforts, warning that would make it more difficult to catch emerging and potentially dangerous new variants.
He called for countries to immunize their most vulnerable populations, including health workers and people over 60, saying that hundreds of millions remain unvaccinated and at risk of severe disease and death.
Tedros said that while more than 1.2 billion COVID-19 vaccines have been administered globally, the average immunization rate in poor countries is about 13%.
If rich countries are vaccinating children from as young as 6 months old and planning to do further rounds of vaccination, it is incomprehensible to suggest that lower-income countries should not vaccinate and boost their most at risk (people), he said.
According to figures compiled by Oxfam and the People's Vaccine Alliance, fewer than half of the 2.1 billion vaccines promised to poorer countries by the Group of Seven large economies have been delivered.
Earlier this month, the United States authorized COVID-19 vaccines for infants and preschoolers, rolling out a national immunization plan targeting 18 million of the youngest children. American regulators also recommended that some adults get updated boosters in the fall that match the latest coronavirus variants.
Follow APs coverage of the pandemic at https://apnews.com/hub/coronavirus-pandemic
Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection | NEJM nejm.org
