http://www.mediterranee-infection.com/wp-content/uploads/2020/04/Abstract_Raoult_EarlyTrtCovid19_09042020_vD1v.pdfABSTRACTBackground In a recent survey, most physicians worldwide considered that hydroxychloroquine (HCQ) and azithromycin (AZ) are the two most effective drugs among available molecules against COVID-19. Nevertheless, to date, one preliminary clinical trial only has demonstrated its efficacy on the viral load. Additionally, a clinical study including 80 patients was published, and in vitro efficiency of this association was demonstrated. Methods The study was performed at IHU Méditerranée Infection, Marseille, France. A cohort of 1061 COVID-19 patients, treated for at least 3 days with the HCQ-AZ combination and a follow-up of at least 9 days was investigated. Endpoints were death, worsening and viral shedding persistence. Findings From March 3rd to April 9th, 2020, 59,655 specimens from 38,617 patients were tested for COVID-19 by PCR. Of the 3,165 positive patients placed in the care of our institute, 1061 previously unpublished patients met our inclusion criteria. Their mean age was 43.6 years old and 492 were male (46.4%). No cardiac toxicity was observed. A good clinical outcome and virological cure was obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage at completion of treatment was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < 10-2) but viral culture was negative at day 10 and all but one were PCR-cleared at day 15. A poor outcome was observed for 46 patients (4.3%); 10 were transferred to intensive care units, 5 patients died (0.47%) (74-95 years old) and 31 required 10 days of hospitalization or more. Among this group, 25 patients are now cured and 16 are still hospitalized (98% of patients cured so far). Poor clinical outcome was significantly associated to older age (OR 1.11), initial higher severity (OR 10.05) and low hydroxychloroquine serum concentration. In addition, both poor clinical and virological outcomes were associated to the use of selective beta-blocking agents and angiotensin II receptor blockers (P<0.05). Mortality was significantly lower in patients who had received >3 days of HCQ-AZ than in patients treated with other regimens both at IHU and in all Marseille public hospitals (p< 10-2). Interpretation The HCQ-AZ combination, when started immediately after diagnosis, is a safe and efficient treatment for COVID-19, with a mortality rate of 0.5%, in elderly patients. It avoids worsening and clears virus persistence and contagiosity in most cases.
This contradicts to today's WSJ article: Chinese Doctors Questio
Early champions of chloroquine, physicians there now find no clear evidence it works
BY JEREMY PAGE
WUHAN, China—Chinese doctors who have for months treated patients on the front lines of China’s fight against the new coronavirus offered a sobering assessment of the potential treatments, saying they hadn’t seen clear evidence that drugs such as chloroquine were effective.
One doctor, however, said he saw some promise for Kaletra— an antiretroviral drug for HIV.
In hospital interviews arranged Thursday by government authorities in Wuhan, the central Chinese city of 11 million where the new coronavirus crisis erupted late last year, doctors called for further research into the use of chloroquine, an antimalarial drug.
The doctors also cautioned that some recovered patients had tested positive again, while expressing concern about asymptomatic cases, dozens of which have been disclosed in recent days across China.
The assessment from doctors came one day after Chinese authorities eased their lockdown of Wuhan, and as the U.S. braces in the coming days for what is expected to be the worst of its surge in infections.
Chloroquine has been the subject of fierce debate within the U.S. administration. In recent days, President Trump has advised even those without symptoms to take the drug, in defiance of advice from public-health experts and some of his own medical advisers.
White House trade adviser Peter Navarro has cited a study from Wuhan, among other evidence, to argue for the federal government to distribute its stockpile of one form of the drug—hydroxychloroquine—to hard-hit areas of the U.S.
Zhang Dingyu, the head of Wuhan’s Jinyintan Hospital, which has handled hundreds of coronavirus cases since December, said the evidence on chloroquine was so far inconclusive.
“Some patients took it by themselves, and after taking it, there were good and bad” results, Dr. Zhang said on Thursday, adding that some patients hadn’t tested negative even seven to 10 days after taking the drug. “There’s no scientific conclusion.”
He expressed concern too about the drug’s recommended dosage. Local health authorities warned in February that an overdose of chloroquine
could be fatal.
At the peak of the epidemic in Wuhan, Dr. Zhang said Jinyintan Hospital was treating as many as 500 patients. It still has 123 patients, of which three were in serious condition on Thursday. None was in intensive care, he said.
While Dr. Zhang expressed uncertainty about chloroquine, he said Kaletra—a drug made by U.S. pharmaceutical giant AbbVie Inc. that blocks the enzymes some viruses need to replicate—appeared to have been effective with patients and infected colleagues, even though a recent study concluded it didn’t work.
Desperation and the lack of a proven cure have prompted doctors around the world to experiment with remedies that haven’t yet passed clinical trials.
The U.S. Food and Drug Ad- ministration on March 28 authorized the emergency use of chloroquine phosphate and hydroxychloroquine in hospitalized coronavirus patients who weren’t able to participate in a clinical trial. That allowed the government to distribute millions of doses donated by drug companies.
Zhang Junjian, a doctor who ran a field hospital in Wuhan that treated more than 1,700 coronavirus cases, said in a separate group interview on Thursday that 20 to 30 patients had been treated with chloroquine— with the patients’ permission— but it was unclear if the drug was effective.
Given the drug’s unproven effects, “we were extremely careful,” said Dr. Zhang, who is vice president of Wuhan’s Zhongnan hospital, another institution that treated thousands of coronavirus cases. “You can’t see any difference between it and other treatments.”
Dr. Zhang, the Jinyintan Hospital chief, said that several of his patients—and three of his infected colleagues—had taken Kaletra.
“After taking it, the changes in their entire lungs were really dramatic,” he said, adding that none of them needed critical care. “If I had a chance to do things again, I would definitely have patients take this drug within three to five days of getting sick.”
A study published in March in the New England Journal of Medicine, based on a test on severe coronavirus cases at Jinyintan, concluded that Kaletra wasn’t effective. But Jinyintan’s Dr. Zhang said supplementary data in the study suggested it had potential.
Dr. Zhang Dingyu, left, speaking in Wuhan about his hospital’s experience with coronavirus cases. QIANWEI ZHANG/THE WALL STREET JOURNAL
Many of the cases at Jinyintan took Kaletra in conjunction with bismuth subcitrate potassium, which had also been effective, he said. Bismuth subcitrate is used in combination with other drugs to treat a common bacterial stomach infection.
Dr. Zhang of Jinyintan also recommended convalescent plasma treatment, which involves transfusing blood plasma from someone who has recovered from the coronavirus into someone who is sick with the virus, in hopes that the donor’s antibodies help the recipient recover.
The FDA says the treatment hasn’t yet been shown to be safe and effective for Covid-19, the disease caused by the coronavirus, but the agency approved its emergency use on a case-by-case basis in March and issued broader recommendations on its use and study on Wednesday.
The Chinese doctors said that 34 of their patients had tested positive again after recovering and being discharged, but they suspected that was because of flawed tests giving false negative results, rather than the patients having been reinfected.
Most worrying was a small number of patients—still in hospitals—who had been infected for several weeks, including several for more than 60 days, said Dr. Zhang of Jinyintan. Another focus of concern, he said, was the number of asymptomatic cases and their level of infectiousness.
“This virus may be with mankind for a long time, so what we need to work on is how to take the next steps,” he said. “We used to pay attention to the flu, AIDS and hand, foot and mouth disease. Now we may need a special ward for this.”
Search for Coronavirus Cure Advances Fast, the Virus Faster
Researchers have a host of projects—new drugs, old drugs, vaccines
For drug companies, there is suddenly only one priority: the coronavirus.
More than 140 experimental drug treatments and vaccines for the coronavirus are in development world-wide, most in early stages, including 11 already in clinical trials, according to Informa Pharma Intelligence.
Counting drugs approved for other diseases, there are 254 clinical trials testing treatments or vaccines for the virus, many spearheaded by universities and government research agencies, with hundreds more trials planned. Researchers have squeezed timelines that usually total months into weeks or even days.
“We have never gone so fast with so many resources in such a short time frame,” said Paul Stoffels, chief scientific officer of Johnson & Johnson.
Even so, for most treatments and vaccines it will be midsummer before human testing reveals whether they are safe to take, not to mention if they work. J& J is excited about a vaccine prospect but won’t be able to start testing it in humans till September. Research
By
Joseph Walker, Peter Loftus
and
Jared S. Hopkins
progress that is remarkable by usual standards remains far behind the racing virus.
Health officials are warning Americans to brace for the most difficult days this week, with the number of infections in the nation’s hardest hit cities expected to peak. In the U.S., more than 10,000 people have died from Covid-19.
It usually takes years to develop a new drug treatment or vaccine. The compounds must be tested in the lab, in animals and extensively in humans. If they succeed, more time is needed to manufacture large numbers of doses.
The urgent, high-speed search is moving on three fronts. One is to get a vaccine that could provide immunity, allowing a return to normalcy.
Among the farthest along is a vaccine hatched by government researchers and Moderna Inc., a biotechnology company in Cambridge, Mass., for which safety testing in humans has begun. If clinical studies succeed, it could be ready for use as soon as early next year, researchers say.
In addition, Inovio Pharmaceuticals Inc. of Plymouth Meeting, Pa., said human trials were starting Monday for an experimental coronavirus vaccine it is developing. Chinese company CanSino Biologics Inc. and a research arm of the Chinese military have started human testing of a vaccine, according to the World Health Organization. In Europe, German company CureVac AG and the University of Oxford are developing vaccines.
Scientists also are exploring whether existing drugs such as hydroxychloroquine for malaria or HIV treatments might work against the coronavirus, and some doctors are already treating patients with hydroxychloroquine. Results of two Chinese studies of Gilead Sciences Inc.’s antiviral remdesivir, previously tested in Ebola, are expected this month. Regeneron Pharmaceuticals Inc. and partner Sanofi SA are testing a rheumatoid arthritis drug against the coronavirus.
On the third front, researchers are hunting for entirely new drugs. Among these efforts, which take longer, are programs to mine the blood of recovered patients for infection- fighting soldiers known as antibodies that can be converted into drugs.
“I think we can find something that, at least, helps people out,” said Derek Lowe, a veteran drug researcher. “Whether any of these things work well enough to get people out of their houses, that’s another question. Maybe it works well enough to reduce the number of people who go on ventilators.”
Johnson & Johnson said it and a division of the Department of Health and Human Services together have committed more than $1 billion of investment to co-fund vaccine research, development, and clinical testing. Other government agencies and universities are also spending on research.
Unlike many drug quests, there’s not necessarily a big payoff at the finish. Some companies have indicated they’ll provide drugs free or at
low cost. Gilead said it won’t charge for 1.5 million doses it has manufactured.
Scenes from labs show the quest from the inside.
One weekend in January, Kizzmekia Corbett rushed to Building 40 on the National Institutes of Health campus in Bethesda, Md.
Dr. Corbett is a researcher at the National Institute of Allergy and Infectious Diseases, or NIAID. For years, she and colleagues have braced for a pandemic, studying bacteria and viruses that popped up around the world to gain a better understanding when a bad one finally came.
Around Jan. 10, she got a cellphone alert with a vital piece of information about a mysterious virus emerging in China. A consortium of researchers including Chinese scientists had published online the virus’s genetic sequence.
That provided its molecular makeup, information needed to craft a vaccine. It also indicated the new virus belonged to a well-known family, the coronaviruses. Named for the crown-like spikes protruding from their surface, coronaviruses had caused two deadly outbreaks since 2002: severe acute respiratory syndrome, or SARS, and Middle East respiratory syndrome, MERS.
Dr. Corbett and a colleague studied the genetic code— seemingly endless combinations of the letters A, G, C and T, each standing for the chemicals making up DNA. The sequence looked similar to that of the SARS virus. This meant researchers who had investigated a SARS vaccine, which didn’t advance after the epidemic waned, could pursue a similar tack against the new coronavirus.
A vaccine would deliver a disabled spike protein, or the genetic instructions to make a close copy, into the human body. This wouldn’t infect a person but would train the immune system to recognize and attack the virus. If a vaccinated person encountered the virus, antibodies would spring into action and neutralize it.
“We’re lucky that this is a coronavirus because we know what to do,” said Barney Graham, deputy director of the Vaccine Research Center at NI-AID.
As the virus spread in Wuhan, China, and then in other countries, U.S. government researchers searched for a partner to help design and make a vaccine. Dr. Graham reached out to Moderna, which is pioneering a new technology for making vaccines. It uses “messenger” RNA, genetic material that can instruct cells to make proteins able to trigger immune responses.
Like the NIH, Moderna researchers studied the new virus’s genetic sequence and concluded the spike protein would be the part to target. By Monday, Jan. 13, the NIAID and Moderna agreed on a vaccine design. Moderna made a small batch for testing. Dr. Corbett and colleagues started testing it in mice on Feb. 4. Two weeks later, initial results showed it elicited antibodies to coronavirus in the blood.
Months of testing in humans would be necessary.. Moderna retrofitted equipment at its plant outside Boston, and by Feb. 25 the NIAID was ready to recruit healthy volunteers.
Champagne moment
One morning the following month, George Yancopoulos, chief scientific officer at Regeneron in Tarrytown, N.Y., texted his head of infectious disease research. “Good luck today,” he wrote. “The world is sort of maybe depending on you ;).”
It was 8:41 a.m. on Saturday, March 14, the latest in a string of weekends consumed by the company’s hunt for a medicine that could knock out the virus. Spearheading the efforts was Christos Kyratsous, drug-discovery chief for infectious diseases, who used a rapid-response platform formed after the 2014 Ebola epidemic in West Africa.
His team collaborated with colleagues who tended some special mice with immune systems genetically engineered to have a human-like response to viruses. Because the mice make antibodies indistinguishable from people’s, researchers working with them can have a compound ready to test in people in months rather than the years it takes to birth a traditional drug from scratch.
The teams had spent weeks collecting antibodies from mice exposed to the coronavirus’s spike protein, in hopes that two of the antibody molecules could be combined into a drug able to stop an infection. They also gathered antibodies from the blood of recovered coronavirus patients.
Experiments to see whether these killed the virus
in test tubes were being finished up that March Saturday.
“You can come now,” Dr. Kyratsous texted Dr. Yancopoulos at 2:45 p.m. Dr. Yancopoulos got off a conference call and walked to the lab. As he entered the lab and saw Dr. Kyratsous smiling, he texted a colleague to bring a bottle of champagne.
Data showed they had found hundreds of antibodies that blocked the virus from entering cells. If it couldn’t enter cells, it couldn’t replicate. A treatment was still far away—but now was in sight. The champagne popped open.
“My head was in a rush: ‘We’ve got it,’ ” Regeneron Chief Executive Leonard Schleifer recalls thinking after his chief scientific officer gave him the details. “The world is starting to fall apart, and if we can just hold on, in that lab, in those tubes, is a cure.”
Regeneron said it would choose the best two antibodies for a drug in April and start clinical trials by early summer. It is preparing to make hundreds of thousands of doses a month by the summer’s end. Getting the drug on the market isn’t assured. Clinical trials showing the treatment is both effective and safe could take months. These are the stages where so many medicines fail even after they show promising test-tube and animal results.
Testing
Neal Browning was scrolling through his Facebook feed in early March when a friend’s post caught his eye.
Mr. Browning is a network engineer at Microsoft Corp. living in the Seattle suburb of Bothell, Wash., not far from one of the country’s earliest and worst coronavirus outbreaks. He also lives close to the research center doing a human study of the vaccine that Moderna and the NIAID are developing.
The research center, Kaiser Permanente Washington Health Research Institute, was urgently seeking healthy volunteers to test the experimental vaccine’s safety. Mr. Browning’s Facebook friend knew of the recruitment effort. After Mr. Browning expressed concern about the virus, the friend texted him details of the trial.
Many medical facilities across the U.S. are seeking people to test the safety of potential coronavirus drugs or vaccines. To make way, they are suspending trials of other medicines, clearing space for coronavirus study subjects and assigning data-entry workers, pharmacists and other staff to deal with the paperwork.
Massachusetts General Hospital, one day after agreeing to test Gilead’s remdesivir, walked federal health officials through how it planned to conduct the trial. It did so by phone for safety reasons and because time was short, said Libby Hohmann, who oversees the hospital’s clinical-trial effort.
That evening, Dr. Hohmann assembled about a dozen pharmacists, researchers and physicians in a conference room to parcel out trial’s tasks, such as collecting blood samples and tracking patients once discharged.
To save time, they skipped typical pretrial exercises such as training the staff in showing hospital doctors and nurses the way to administer the drug. “We’re sort of doing those on the fly,” Dr. Hohmann said.
Since the trial began March 15, Mass General has enrolled 35 subjects. Among them is a man in his 40s who agreed to be in the study just before nurses inserted a breathing tube down his throat because of respiratory problems from the virus, Dr. Hohmann said. He is now stable, she said.
For the test of Moderna’s vaccine, Mr. Browning, the Microsoft engineer, showed up at the Kaiser research institute in downtown Seattle on March 16, becoming only the second volunteer.
It had been just nine weeks since researchers selected a section of the virus’s genetic sequence to target, an unusually short period. Even so, the trial is unlikely to have preliminary results until summer, followed by more testing required that would push the vaccine’s availability out about 12 to 18 months, according to the NIAID.
After his shot, Mr. Browning stayed for about an hour so the staff could make sure he didn’t have any side effects. He drove home and worked that afternoon helping Microsoft configure network firewalls to accommodate a surge in employees working remotely, until the threat posed by the virus can be quashed.
详情请看我博客中介绍瑞德西维的那篇文章。
最好开放羟氯喹和阿齐霉素的处方权，暂时变成 OVER THE COUNTER。感觉有症状就先开始吃，再去检测病毒。这样早几个小时有的时候也是决定LIFE OR DEATH。
就收到他们礼貌性的EMAIL回复，估计都没人看。这帮政府官员！
一个病毒颗粒侵入一个细胞，几个小时内能变成几百个新的病毒颗粒。这种速度，几天内所有带受体的细胞都已经感染了。这时候用药为时已晚。
每天10mg（只算锌），可以较长时间服用，作为预防用药。
一旦有感染症状，x4。
https://www.mayoclinic.org/drugs-supplements-zinc/art-20366112
https://www.webmd.com/vitamins/ai/ingredientmono-982/zinc
Early champions of chloroquine, physicians there now find no clear evidence it works
BY JEREMY PAGE
WUHAN, China—Chinese doctors who have for months treated patients on the front lines of China’s fight against the new coronavirus offered a sobering assessment of the potential treatments, saying they hadn’t seen clear evidence that drugs such as chloroquine were effective.
One doctor, however, said he saw some promise for Kaletra— an antiretroviral drug for HIV.
In hospital interviews arranged Thursday by government authorities in Wuhan, the central Chinese city of 11 million where the new coronavirus crisis erupted late last year, doctors called for further research into the use of chloroquine, an antimalarial drug.
The doctors also cautioned that some recovered patients had tested positive again, while expressing concern about asymptomatic cases, dozens of which have been disclosed in recent days across China.
The assessment from doctors came one day after Chinese authorities eased their lockdown of Wuhan, and as the U.S. braces in the coming days for what is expected to be the worst of its surge in infections.
Chloroquine has been the subject of fierce debate within the U.S. administration. In recent days, President Trump has advised even those without symptoms to take the drug, in defiance of advice from public-health experts and some of his own medical advisers.
White House trade adviser Peter Navarro has cited a study from Wuhan, among other evidence, to argue for the federal government to distribute its stockpile of one form of the drug—hydroxychloroquine—to hard-hit areas of the U.S.
Zhang Dingyu, the head of Wuhan’s Jinyintan Hospital, which has handled hundreds of coronavirus cases since December, said the evidence on chloroquine was so far inconclusive.
“Some patients took it by themselves, and after taking it, there were good and bad” results, Dr. Zhang said on Thursday, adding that some patients hadn’t tested negative even seven to 10 days after taking the drug. “There’s no scientific conclusion.”
He expressed concern too about the drug’s recommended dosage. Local health authorities warned in February that an overdose of chloroquine
could be fatal.
At the peak of the epidemic in Wuhan, Dr. Zhang said Jinyintan Hospital was treating as many as 500 patients. It still has 123 patients, of which three were in serious condition on Thursday. None was in intensive care, he said.
While Dr. Zhang expressed uncertainty about chloroquine, he said Kaletra—a drug made by U.S. pharmaceutical giant AbbVie Inc. that blocks the enzymes some viruses need to replicate—appeared to have been effective with patients and infected colleagues, even though a recent study concluded it didn’t work.
Desperation and the lack of a proven cure have prompted doctors around the world to experiment with remedies that haven’t yet passed clinical trials.
The U.S. Food and Drug Ad- ministration on March 28 authorized the emergency use of chloroquine phosphate and hydroxychloroquine in hospitalized coronavirus patients who weren’t able to participate in a clinical trial. That allowed the government to distribute millions of doses donated by drug companies.
Zhang Junjian, a doctor who ran a field hospital in Wuhan that treated more than 1,700 coronavirus cases, said in a separate group interview on Thursday that 20 to 30 patients had been treated with chloroquine— with the patients’ permission— but it was unclear if the drug was effective.
Given the drug’s unproven effects, “we were extremely careful,” said Dr. Zhang, who is vice president of Wuhan’s Zhongnan hospital, another institution that treated thousands of coronavirus cases. “You can’t see any difference between it and other treatments.”
Dr. Zhang, the Jinyintan Hospital chief, said that several of his patients—and three of his infected colleagues—had taken Kaletra.
“After taking it, the changes in their entire lungs were really dramatic,” he said, adding that none of them needed critical care. “If I had a chance to do things again, I would definitely have patients take this drug within three to five days of getting sick.”
A study published in March in the New England Journal of Medicine, based on a test on severe coronavirus cases at Jinyintan, concluded that Kaletra wasn’t effective. But Jinyintan’s Dr. Zhang said supplementary data in the study suggested it had potential.
Dr. Zhang Dingyu, left, speaking in Wuhan about his hospital’s experience with coronavirus cases. QIANWEI ZHANG/THE WALL STREET JOURNAL
Many of the cases at Jinyintan took Kaletra in conjunction with bismuth subcitrate potassium, which had also been effective, he said. Bismuth subcitrate is used in combination with other drugs to treat a common bacterial stomach infection.
Dr. Zhang of Jinyintan also recommended convalescent plasma treatment, which involves transfusing blood plasma from someone who has recovered from the coronavirus into someone who is sick with the virus, in hopes that the donor’s antibodies help the recipient recover.
The FDA says the treatment hasn’t yet been shown to be safe and effective for Covid-19, the disease caused by the coronavirus, but the agency approved its emergency use on a case-by-case basis in March and issued broader recommendations on its use and study on Wednesday.
The Chinese doctors said that 34 of their patients had tested positive again after recovering and being discharged, but they suspected that was because of flawed tests giving false negative results, rather than the patients having been reinfected.
Most worrying was a small number of patients—still in hospitals—who had been infected for several weeks, including several for more than 60 days, said Dr. Zhang of Jinyintan. Another focus of concern, he said, was the number of asymptomatic cases and their level of infectiousness.
“This virus may be with mankind for a long time, so what we need to work on is how to take the next steps,” he said. “We used to pay attention to the flu, AIDS and hand, foot and mouth disease. Now we may need a special ward for this.”
不是片剂量。剂型不同，锌当量不一样。样
比如，我用Zinc Picolinate 50mg/Capsule，
50mg zinc picolinate is eqivalent to 10.6mg elemental zincSearch for Coronavirus Cure Advances Fast, the Virus Faster
Researchers have a host of projects—new drugs, old drugs, vaccines
For drug companies, there is suddenly only one priority: the coronavirus.
More than 140 experimental drug treatments and vaccines for the coronavirus are in development world-wide, most in early stages, including 11 already in clinical trials, according to Informa Pharma Intelligence.
Counting drugs approved for other diseases, there are 254 clinical trials testing treatments or vaccines for the virus, many spearheaded by universities and government research agencies, with hundreds more trials planned. Researchers have squeezed timelines that usually total months into weeks or even days.
“We have never gone so fast with so many resources in such a short time frame,” said Paul Stoffels, chief scientific officer of Johnson & Johnson.
Even so, for most treatments and vaccines it will be midsummer before human testing reveals whether they are safe to take, not to mention if they work. J& J is excited about a vaccine prospect but won’t be able to start testing it in humans till September. Research
By
Joseph Walker, Peter Loftus
and
Jared S. Hopkins
progress that is remarkable by usual standards remains far behind the racing virus.
Health officials are warning Americans to brace for the most difficult days this week, with the number of infections in the nation’s hardest hit cities expected to peak. In the U.S., more than 10,000 people have died from Covid-19.
It usually takes years to develop a new drug treatment or vaccine. The compounds must be tested in the lab, in animals and extensively in humans. If they succeed, more time is needed to manufacture large numbers of doses.
The urgent, high-speed search is moving on three fronts. One is to get a vaccine that could provide immunity, allowing a return to normalcy.
Among the farthest along is a vaccine hatched by government researchers and Moderna Inc., a biotechnology company in Cambridge, Mass., for which safety testing in humans has begun. If clinical studies succeed, it could be ready for use as soon as early next year, researchers say.
In addition, Inovio Pharmaceuticals Inc. of Plymouth Meeting, Pa., said human trials were starting Monday for an experimental coronavirus vaccine it is developing. Chinese company CanSino Biologics Inc. and a research arm of the Chinese military have started human testing of a vaccine, according to the World Health Organization. In Europe, German company CureVac AG and the University of Oxford are developing vaccines.
Scientists also are exploring whether existing drugs such as hydroxychloroquine for malaria or HIV treatments might work against the coronavirus, and some doctors are already treating patients with hydroxychloroquine. Results of two Chinese studies of Gilead Sciences Inc.’s antiviral remdesivir, previously tested in Ebola, are expected this month. Regeneron Pharmaceuticals Inc. and partner Sanofi SA are testing a rheumatoid arthritis drug against the coronavirus.
On the third front, researchers are hunting for entirely new drugs. Among these efforts, which take longer, are programs to mine the blood of recovered patients for infection- fighting soldiers known as antibodies that can be converted into drugs.
“I think we can find something that, at least, helps people out,” said Derek Lowe, a veteran drug researcher. “Whether any of these things work well enough to get people out of their houses, that’s another question. Maybe it works well enough to reduce the number of people who go on ventilators.”
Johnson & Johnson said it and a division of the Department of Health and Human Services together have committed more than $1 billion of investment to co-fund vaccine research, development, and clinical testing. Other government agencies and universities are also spending on research.
Unlike many drug quests, there’s not necessarily a big payoff at the finish. Some companies have indicated they’ll provide drugs free or at
low cost. Gilead said it won’t charge for 1.5 million doses it has manufactured.
Scenes from labs show the quest from the inside.
One weekend in January, Kizzmekia Corbett rushed to Building 40 on the National Institutes of Health campus in Bethesda, Md.
Dr. Corbett is a researcher at the National Institute of Allergy and Infectious Diseases, or NIAID. For years, she and colleagues have braced for a pandemic, studying bacteria and viruses that popped up around the world to gain a better understanding when a bad one finally came.
Around Jan. 10, she got a cellphone alert with a vital piece of information about a mysterious virus emerging in China. A consortium of researchers including Chinese scientists had published online the virus’s genetic sequence.
That provided its molecular makeup, information needed to craft a vaccine. It also indicated the new virus belonged to a well-known family, the coronaviruses. Named for the crown-like spikes protruding from their surface, coronaviruses had caused two deadly outbreaks since 2002: severe acute respiratory syndrome, or SARS, and Middle East respiratory syndrome, MERS.
Dr. Corbett and a colleague studied the genetic code— seemingly endless combinations of the letters A, G, C and T, each standing for the chemicals making up DNA. The sequence looked similar to that of the SARS virus. This meant researchers who had investigated a SARS vaccine, which didn’t advance after the epidemic waned, could pursue a similar tack against the new coronavirus.
A vaccine would deliver a disabled spike protein, or the genetic instructions to make a close copy, into the human body. This wouldn’t infect a person but would train the immune system to recognize and attack the virus. If a vaccinated person encountered the virus, antibodies would spring into action and neutralize it.
“We’re lucky that this is a coronavirus because we know what to do,” said Barney Graham, deputy director of the Vaccine Research Center at NI-AID.
As the virus spread in Wuhan, China, and then in other countries, U.S. government researchers searched for a partner to help design and make a vaccine. Dr. Graham reached out to Moderna, which is pioneering a new technology for making vaccines. It uses “messenger” RNA, genetic material that can instruct cells to make proteins able to trigger immune responses.
Like the NIH, Moderna researchers studied the new virus’s genetic sequence and concluded the spike protein would be the part to target. By Monday, Jan. 13, the NIAID and Moderna agreed on a vaccine design. Moderna made a small batch for testing. Dr. Corbett and colleagues started testing it in mice on Feb. 4. Two weeks later, initial results showed it elicited antibodies to coronavirus in the blood.
Months of testing in humans would be necessary.. Moderna retrofitted equipment at its plant outside Boston, and by Feb. 25 the NIAID was ready to recruit healthy volunteers.
Champagne moment
One morning the following month, George Yancopoulos, chief scientific officer at Regeneron in Tarrytown, N.Y., texted his head of infectious disease research. “Good luck today,” he wrote. “The world is sort of maybe depending on you ;).”
It was 8:41 a.m. on Saturday, March 14, the latest in a string of weekends consumed by the company’s hunt for a medicine that could knock out the virus. Spearheading the efforts was Christos Kyratsous, drug-discovery chief for infectious diseases, who used a rapid-response platform formed after the 2014 Ebola epidemic in West Africa.
His team collaborated with colleagues who tended some special mice with immune systems genetically engineered to have a human-like response to viruses. Because the mice make antibodies indistinguishable from people’s, researchers working with them can have a compound ready to test in people in months rather than the years it takes to birth a traditional drug from scratch.
The teams had spent weeks collecting antibodies from mice exposed to the coronavirus’s spike protein, in hopes that two of the antibody molecules could be combined into a drug able to stop an infection. They also gathered antibodies from the blood of recovered coronavirus patients.
Experiments to see whether these killed the virus
in test tubes were being finished up that March Saturday.
“You can come now,” Dr. Kyratsous texted Dr. Yancopoulos at 2:45 p.m. Dr. Yancopoulos got off a conference call and walked to the lab. As he entered the lab and saw Dr. Kyratsous smiling, he texted a colleague to bring a bottle of champagne.
Data showed they had found hundreds of antibodies that blocked the virus from entering cells. If it couldn’t enter cells, it couldn’t replicate. A treatment was still far away—but now was in sight. The champagne popped open.
“My head was in a rush: ‘We’ve got it,’ ” Regeneron Chief Executive Leonard Schleifer recalls thinking after his chief scientific officer gave him the details. “The world is starting to fall apart, and if we can just hold on, in that lab, in those tubes, is a cure.”
Regeneron said it would choose the best two antibodies for a drug in April and start clinical trials by early summer. It is preparing to make hundreds of thousands of doses a month by the summer’s end. Getting the drug on the market isn’t assured. Clinical trials showing the treatment is both effective and safe could take months. These are the stages where so many medicines fail even after they show promising test-tube and animal results.
Testing
Neal Browning was scrolling through his Facebook feed in early March when a friend’s post caught his eye.
Mr. Browning is a network engineer at Microsoft Corp. living in the Seattle suburb of Bothell, Wash., not far from one of the country’s earliest and worst coronavirus outbreaks. He also lives close to the research center doing a human study of the vaccine that Moderna and the NIAID are developing.
The research center, Kaiser Permanente Washington Health Research Institute, was urgently seeking healthy volunteers to test the experimental vaccine’s safety. Mr. Browning’s Facebook friend knew of the recruitment effort. After Mr. Browning expressed concern about the virus, the friend texted him details of the trial.
Many medical facilities across the U.S. are seeking people to test the safety of potential coronavirus drugs or vaccines. To make way, they are suspending trials of other medicines, clearing space for coronavirus study subjects and assigning data-entry workers, pharmacists and other staff to deal with the paperwork.
Massachusetts General Hospital, one day after agreeing to test Gilead’s remdesivir, walked federal health officials through how it planned to conduct the trial. It did so by phone for safety reasons and because time was short, said Libby Hohmann, who oversees the hospital’s clinical-trial effort.
That evening, Dr. Hohmann assembled about a dozen pharmacists, researchers and physicians in a conference room to parcel out trial’s tasks, such as collecting blood samples and tracking patients once discharged.
To save time, they skipped typical pretrial exercises such as training the staff in showing hospital doctors and nurses the way to administer the drug. “We’re sort of doing those on the fly,” Dr. Hohmann said.
Since the trial began March 15, Mass General has enrolled 35 subjects. Among them is a man in his 40s who agreed to be in the study just before nurses inserted a breathing tube down his throat because of respiratory problems from the virus, Dr. Hohmann said. He is now stable, she said.
For the test of Moderna’s vaccine, Mr. Browning, the Microsoft engineer, showed up at the Kaiser research institute in downtown Seattle on March 16, becoming only the second volunteer.
It had been just nine weeks since researchers selected a section of the virus’s genetic sequence to target, an unusually short period. Even so, the trial is unlikely to have preliminary results until summer, followed by more testing required that would push the vaccine’s availability out about 12 to 18 months, according to the NIAID.
After his shot, Mr. Browning stayed for about an hour so the staff could make sure he didn’t have any side effects. He drove home and worked that afternoon helping Microsoft configure network firewalls to accommodate a surge in employees working remotely, until the threat posed by the virus can be quashed.