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Search for key to beat virus

Bay Area at center of many promising treatment studies
By Peter Fimrite and J.D. Morris

The frenetic search for the miracle that will rid the world of COVID-19 is branching out in a thousand directions, and a large part of the microbial treasure hunt is going on in the Bay Area, where major progress has been made in the 100 days since residents were ordered to shelter in place.

Scientists at universities, laboratories, biotechnology companies and drug manufacturers are combing through blood plasma taken from infected patients for secrets that will help them fight the disease.

The key is likely a superstrength antibody found in some patients. But researchers must first figure out how those antibodies work and how they can be harnessed and used to stop the many health problems associated with COVID-19, particularly acute respiratory distress syndrome, or ARDS, which has killed more people than any other complication connected to the disease.

Other developments showing promise include injections of mesenchymal stem cells, found in bone marrow and umbilical cords, that doctors are studying to battle inflammation caused by ARDS. And a steroid called dexamethasone reduced the number of deaths by halting the overreactive immune responses in seriously ill patients in the United Kingdom.

In all, more than 130 vaccines and 220 treatments are being tested worldwide.

What follows is a list of some of the most promising elixirs, medications and vaccines with ties to the Bay Area:

Antibodies and immunity

Monoclonal antibodies / Vir Biotechnology, San Francisco: Scientists at Vir and several institutions, including Stanford and UCSF, are studying monoclonal antibodies, which are clones of coronavirusfighting antibodies produced by COVID-19 patients.

The idea is to utilize these “neutralizing antibodies” — which bind to the virus’ crown-like spikes — and prevent them from entering and hijacking human cells.

Only about 5% of coronavirus patients have these superstrength antibodies, and those people are believed to be immune to a second attack.

The trick for scientists at Vir is to identify these neutralizing antibodies, harvest, purify and clone them. If they succeed, the resulting monoclones could then be used to inoculate people and — it is hoped — give them long-term immunity against the coronavirus. The company recently signed a deal with Samsung Biologics, in South Korea, to scale up production of a temporary vaccine in the fall after clinical trials are complete.
Another monoclonal antibody, leronlimab, is being studied in coronavirus clinical trials by its Washington state drugmaker, CytoDyn. The company’s chief medical officer is in San Francisco, and the company that does laboratory tests of leronlimab is in San Carlos.

Interferon-lambda / Stanford University: Doctors at Stanford are running a trial to see if interferon- lambda, which is administered by injection, helps patients in the early stages of COVID-19. Interferon- lambda is a manufactured version of a naturally occurring protein that has been used to treat hepatitis. Stanford doctors hope it will boost the immune system response to coronavirus infections.

Dr. Upinder Singh, a Stanford infectious-disease expert, said the trial has enrolled more than 50 patients and is halfway finished. “We have noted that patients tolerate the drug very well,” she said.

Mesenchymal stem cells / UCSF and UC Davis Medical Center: UCSF Dr. Michael Matthay is leading a study about whether a kind of stem cell found in bone marrow can help patients with ARDS. Matthay hopes that the stem cells can help reduce the inflammation associated with some of ARDS’ most dire respiratory symptoms, and help patients’ lungs to recover.

Matthay is aiming to enroll 120 patients in San Francisco, the UC Davis Medical Center in Sacramento and hospitals in a handful of other states. He said the trial, which includes a small number ARDS patients who don’t have COVID-19, should have results within a year. So far 17 patients are enrolled in the trial, most of them in San Francisco.

Antiviral drugs

Remdesivir / Gilead Sciences (Foster City): Remdesivir, once conceived as a potential treatment for ebola, was the first drug to show some promise in treating COVID-19 patients. The drug interferes with the process through which the virus replicates itself. A large study led by the federal government generated excitement in late April when officials said hospitalized patients who received remdesivir intravenously recovered faster than those who received a placebo.

A later study looking at dosage showed some benefit for moderately ill COVID-19 patients who received remdesivir for five days, but improvement among those who got it for 10 days was not statistically significant. Gilead, a drug company, recently announced that it will soon launch another clinical trial to see how remdesivir works on 50 pediatric patients, from newborns to teenagers, with moderate to severe COVID-19 symptoms. More than 30 locations in the U.S. and Europe will be involved in the trial, the company said.

Favipiravir / Fujifilm Toyama Chemical (Stanford University): This antiviral drug, developed in 2014 by a subsidiary of the Japanese film company to treat influenza, is undergoing numerous clinical studies worldwide, including a Stanford University trial that began this month. Unlike remdesivir, it can be administered orally, so it can be used to treat patients early in the disease, before hospitalization is necessary.

Stanford epidemiologists want to see if favipiravir, which has shown promising results in other trials, prevents the coronavirus from replicating in human cells, halts the shedding of the virus and reduces the severity of infection. The Stanford study, the only outpatient trial for this drug in the nation, is enrolling 120 people who have been diagnosed with COVID-19 within the past 72 hours. Half of them will get a placebo. People can enroll by emailing Anti-inflammatory drugs

Colchicine / UCSF (San Francisco and New York): The anti-inflammatory drug commonly used to treat gout flareups is being studied in the U.S. by scientists at UCSF and New York University. The drug shortcircuits inflammation by decreasing the body’s production of certain proteins, and researchers hope that it will reduce lung complications and prevent deaths from COVID-19. About 6,000 patients are receiving colchicine or a placebo during the clinical trial, dubbed Colcorona, which began in March and is expected to be completed in September.

Selinexor / Kaiser Permanente: Kaiser hospitals in San Francisco, Oakland and Sacramento are studying selinexor, an anticancer drug that blocks a key protein in the cellular machinery for DNA processing, as a potential COVID-19 treatment. The drug has both antiviral and anti-inflammatory properties, and it’s administered orally, according to Kaiser’s Dr. Jacek Skarbinski. The trial aims to enroll 250 patients with severe symptoms at Kaiser and other hospitals that are participating nationwide.


VXA-COV2-1 / Vaxart, South San Francisco: The biotechnology company Vaxart is testing this drug to see if it is as effective at controlling COVID-19 as trials have shown it to be against influenza. VXACOV2-1, the only potential vaccine in pill form, uses the genetic code of the coronavirus to trigger a defensive response in mucous membranes. The hope is that the newly fortified membranes will prevent the virus from entering the body.

“It’s the only vaccine (candidate) that activates the first line of defense, which is the mucosa,” said Andrei Floroiu, Vaxart’s chief executive, noting that intravenous vaccines kill the virus after it is inside the body. “Our vaccine may prevent you from getting infected at all.”

The drug was effective against influenza and norovirus in trials and appears to work on laboratory animals, Floroiu said. He expects trials of VXA-COV2-1 on humans to begin later this summer.

VaxiPatch / Verndari (Napa and UC Davis Medical Center): Napa vaccine company Verndari makes a patented adhesive patch that can deliver a vaccine instead of a shot. Now, the company is trying to make a vaccine for COVID-19 that they can administer through that patch. At UC Davis Medical Center in Sacramento, Verndari researchers are developing a potential vaccine that relies on the coronavirus’ spike-shaped protein. When injected into a person, the substance would ideally train their body to recognize the virus and fight it off without becoming ill.

A spokeswoman told The Chronicle that the company’s preclinical tests have shown “early, positive data in developing an immune response.” Verndari hopes to move into the next phase of testing in the coming weeks and start clinical trials in humans this year.

If the vaccine is proved effective and safe, patients could receive it through the mail, according to company CEO Dr. Daniel Henderson. The patch would leave a temporary mark on the skin that patients could photograph and send to their doctor as proof they have taken the vaccine, Henderson has said.
Peter Fimrite and J.D. Morris are San Francisco Chronicle staff writers. Email:, Twitter: @pfimrite, @thejdmorris


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