Can COVID-19 protection be found in drugs as simple as medicines containing pseudoephedrine and arthritis? Flaxseed and turmeric extract? Fish oil, ibuprofen, nasal spray, vitamin D?
There is high hope that therapeutic agents are hiding in the medicine cabinet, but evidence remains scarce as research continues. One year into the pandemic, the U.S. Food and Drug Administration approved just one drug to treat COVID-19, and the consequences are moderate. A few others, mimicking the work of natural antibodies, have obtained permission for emergency use, but that’s not bad either.
Behind the scenes, with deaths increasing and clocks ticking, researchers are working ‘with an intense sense of purpose’ to investigate myriad compounds that can stop disease.
The treatment piece of the pandemic puzzle did not capture the imagination of the public – or so much of the public purse – just like the space race for effective vaccines. While the search for therapies is plagued by the lack of laser focus and high-level organization that has driven shots so fast in the arms, the development of therapeutic agents that can tame COVID-19 is essential to saving lives, researchers say. Millions have not had access to vaccines for many months – or longer. Some cannot, or do not want to, be vaccinated. A small fraction of vaccinated people may not respond to the sting.
And many expect COVID-19 to be with humanity forever.
“We are looking for therapeutic agents to help people who are not sick enough to get to the hospital. This is the vast majority of people who get COVID,” said Prasanna Jagannathan, an infectious disease specialist at Stanford Medicine and an assistant. professor of microbiology and immunology.
Most patients recovered at home without much drama, but an alarming number – presumably well on their way to recovery – were suddenly struck by devastating waves of symptoms that gave the phenomenon a name: ‘The second week of COVID crash. ‘
“We’ve seen what happened with this recent boom,” said Judith S. Currier, head of UCLA’s infectious diseases division in the medical department. ‘When people are diagnosed as outpatients, they are told to stay home and wait or see if they get sick. We have an idea which people are at risk of becoming very ill and who should be in the hospital – but this is not perfect. ”
The tricky part of finding a remedy that works early in the infection cycle is finding enough people with fresh COVID-19 diagnoses – long before there is an “accident” or hospitalization needed – to participate in well-designed studies of drugs that can prevent the virus from progressing.
“Our study mantra is, ‘Rise above COVID,'” said Currier, who also chairs the global AIDS Clinical Trials Group, which conducts several COVID trials for the National Institutes of Health. ‘The whole idea is to bring people together to contribute to the answers. We encourage people to think about how they can help advance science – it’s something they can do do. We must be prepared for the future. Participants find the process very rewarding and we are so grateful for their contributions. ”
Those who have been recently diagnosed can find a study to share at www.riseabovecovid.org/en. In Northern California, studies are underway at UC San Francisco, Stanford University, VA Northern California Health Care System, UC Davis and several other sites. In Southern California, they are running at UCLA, USC, UC Irvine, St. Louis. Joseph’s Clinical Research, Riverside Medical Clinic, Loma Linda University Health and several other sites.
“It’s all on the deck,” said Sarah Doernberg, associate professor in the Infectious Diseases Division at UCSF, medical director of Adult Antimicrobial Stewardship at UCSF Medical Center and site investigator for the trial. ‘Many scientists have focused their attention on everything they have done – who probably have not studied coronaviruses – to focus on identifying treatments and understanding the immune response. That piece was really inspiring to see. ”
Today’s tools
Today, there are few tools in the toolbox.
“Unfortunately, there is not so much progress yet,” said Edward Jones-Lopez, an expert in infectious diseases at Keck Medicine of USC. ‘Usually, treatments are first developed for other diseases, and then the vaccines follow later. It happens that the reverse is true for this. ”
The antiviral inhibitor is the only drug so far formally approved by the FDA for the treatment of COVID-19, but it is aimed at patients admitted to the hospital. It can interfere with the reproduction of the virus and can reduce hospital stay by a few days, but it is not a cure.
There are eight other drugs that twist the tongue, receive FDA approval – making it possible to use them before their efficacy is proven in large-scale, randomized clinical trials – but it also does not appear to be a proprietary undertaking. It ranges from the monoclonal antibodies casirivimab and imdevimab, laboratory-made proteins that mimic the immune system’s ability to fight harmful pathogens, to baricitinib, an oral tablet used to treat rheumatoid arthritis by blocking enzyme activity leading to inflammation.
The World Health Organization strongly recommends that corticosteroids – such as dexamethasone, hydrocortisone or prednisone – be administered orally or intravenously to patients with severe and critical COVID-19. Those can suppress the response of the immune system to the virus, which is associated with many deaths.
‘For monoclonal antibodies, we have data from multiple studies suggesting that they reduce the risk of taking on average about two-thirds, early in the course of COVID-9, by about two-thirds, in patients with symptoms, but not yet with serious illness, ”said Saahir Khan, an infectious disease specialist and chief investigator at USC’s trial site in Keck Medicine.
“It is extremely encouraging. The caveat is that some of the new variants of COVID-19 may reduce the activity of antibodies against it, and there are reasonable logistical challenges. It should be given by IV and monitored in a hospital setting. ‘
To get COVID-19 positive patients who do not feel well and just want to curl up in their warm beds from home and to medical sites for intravenous infusions. UCLA has refurbished storage pods in private infusion booths to make the road easier.
“None of this is a silver bullet,” Khan said.
Investigation
But the search for a silver bullet, or a few, continues.
More than 600 drug development programs are in the planning stages, and 420 trials have been reviewed by the FDA. Scientists are looking for electronic health records to see which drugs used frequently – such as those in your medicine chest – can be linked to better COVID-19 outcomes for patients.
The search began in April when the National Institutes of Health launched the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, a public-private partnership to accelerate the development of the most promising treatments and vaccines. Since then, researchers have evaluated hundreds of therapeutic drugs and are trying to find drugs that can do the job via a pill or inhaler, and not just by intravenous infusion.
Among those underway is the SNG001 from Synairgen, an inhaled beta-interferon. This type of remedy helps to reduce inflammation and the immune response of the body.
Jagannathan, from Stanford, is one of the main investigators on interferon, and he likes what he sees.
“We are very excited about this for a number of reasons,” he said. “Interferon seems to play a very important role in the body’s early response to infection. There is evidence that people with a lack of signal have serious illnesses, and early evidence suggests that giving this particular interferon may be beneficial. ‘
A small, early trial in Israel of a protein called EXO-CD24 appears to have helped some with moderate to severe cases of COVID-19.
And then there’s the stuff in your medicine cabinet – and already in your arm.
Fish oil? Vitamin D?
At Vanderbilt University, Cosmin A. Bejan and his colleagues dived into data from electronic health records to see which drugs already in use could be used again as potential candidates for COVID-19.
In findings that surprised even the researchers, people who had recently had a vaccine against pneumonia had a significantly reduced risk of dying from the coronavirus, as well as those who had vaccines against diphtheria and tetanus, as well as those who had been exposed earlier. was to linseed extract, methylprednisolone. acetate, pseudoephedrine, omega-3 fatty acids, turmeric extract, ibuprofen and fluticasone, the active ingredient in Flonase and other nasal sprays for allergies.
“I think the finding that pneumococcal vaccines (as well as other vaccines) save lives in people with COVID-19 is important,” Bejan said in an email. Further randomized clinical trials are needed, he said.
“It would also be great to see the replication of our results through other studies on larger and more heterogeneous study populations,” Bejan added.
Study blood thinner
The ACTIV consortium is also investigating blood thinners – including apixaban, aspirin and heparin – to see if they can prevent life-threatening blood clots in COVID-19 patients, as well as to test medicines already approved for the treatment of other conditions, including risankizumab which was used earlier. treat plaque psoriasis, and lenzilumab, used to treat cancer patients who experience cytokine storm due to their therapies.
The hope is also great for other common compounds, although such hope often goes up.
After much hype about zinc and vitamin C, a study published in the Journal of the American Medical Association found that no individual symptom resolved faster with alone or a combination thereof. The hospitalization figures also did not differ significantly.
Vitamin D also had a moment. In one study, vitamin D deficiency was found in 97% of the seriously ill patients who required ICU admission, but in only 33% of the asymptomatic cases, writes former US surgeon General Richard H. Carmona and co-authors. But a study published in JAMA threw cold water on it and found that a high dose of vitamin D3 did not significantly reduce hospital stay for patients with moderate to severe illness.
Former President Donald Trump has proposed hydroxychloroquine as a panacea, but it appears to be doing more harm than good.
‘A marathon … not a sprint’
The past year has been traumatic, but the chances of surviving COVID-19 have improved significantly since the outbreak of the pandemic, NIH Director Francis S. Collins wrote in a recent blog post.
“This improvement stems from several factors, including the FDA’s emergency authorization for a number of treatments found to be safe and effective for COVID-19,” he wrote. “The quest to save more lives from COVID-19 is not even close yet, and researchers are still working intensively to develop new and better treatments. …
“Our job is clearly a marathon, not a sprint.”