How are hospitals treating COVID?
So far, most drugs repurposed from the medicine cabinet have failed against COVID  from Donald Trumps pick, hydroxychloroquine, to the anti-HIV combination lopinavir/ritonavir. In [severe] cases, hydroxychloroquine can even make things worse, Tong says. Doctors around the world have often faced a harrowing choice between waiting for treatment trials to finish and offering experimental therapies to the dying patients before them in the meantime. Loading Two drugs work well enough that they are now standard in COVID hospital wards, including in Australia: the antiviral remdesivir, formulated to fight Ebola and somewhat effective in stopping the coronavirus replicating in cells, and the inexpensive steroid dexamethasone, which dampens that dangerous immune system overreaction. Dexamethasone is the stand-out, shown to bring down the risk of death by a third for COVID patients on ventilators, and nearly a fifth for those on oxygen therapy (Theres no silver bullet but were very confident that saves lives, Tong says). Remdesivir has had more disappointing results in terms of reducing mortality, Tong says, but is still considered safe. Patients will often get both together in hospitals. Vaccines tell your immune system which antibodies to make to fight off COVID-19; they then gum up the signature spike protein the virus uses to break into cells. But, for someone already infected, or someone with a compromised immune system, doctors can put antibodies directly into the body via transfusion. Before vaccines arrived, this was already being tried by borrowing the immunity (antibodies) still active in the blood plasma of recovered COVID patients. But, despite urgent calls for survivors to donate their plasma and a large rollout in hospitals worldwide, Tong says it has since been found not to help patients as first hoped. ASCOT halted its own test of plasma transfusions in February of this year. Loading Instead, designer antibodies engineered in the lab, known as monoclonals, are proving very effective at stopping patients early on from developing severe disease. Theyre engineered to go after the spike just like the vaccine, Tong says. The treatment is already approved in the United States and Tong says it would be good to see it come to Australia, too. When people test positive who we know are at higher risk of severe disease, those who have [underlying conditions] like diabetes or are older, then we could give it to them proactively. Kelleher says that, as with most of the existing drugs tested on COVID, monoclonals have a long safety record, often cooked up for cancers, hepatitis and autoimmune conditions. They work especially well in patients whose immune system does not kick in strongly against COVID. Eventually, we might be testing a patients initial antibody response and then coming up with the best treatment algorithm from there, Kelleher says. Kirby Institute researchers are part of a global trial testing newly developed monoclonals in places such as Indonesia and South America, with plans to trial designer anti-viral drugs next. But monoclonals are also expensive and difficult to make, Kelleher says.They are given intravenously at present, posing a challenge for delivery to early-stage patients outside a hospital. And some already appear vulnerable to evolving variants of the virus. Although there is some evidence emerging that the more contagious Delta variant also has a higher hospitalisation rate, Tong says overall we dont know if the response to treatment varies by variant. Certainly, therapies focused on dampening the bodys immune response wont be. Not all drugs are aimed at the spike protein though, thats the bit [of the virus that keeps mutating], so they might not be as vulnerable as monoclonals, Kelleher adds. Thats the hope. So far a number of candidates have failed. But Pfizer, which developed one of the mRNA vaccines for COVID, is testing an antiviral pill to stop more severe disease developing, which it hopes to have available by the end of the year. The US government has already agreed to pay Merck & Co. $US1.2 billion ($1.6 billion) for the companys own experimental antiviral molnupiravir if it clears regulators. Preventative nasal sprays that kill the virus as it enters the body via the nose and mouth are also being tested (and the inhaled steroidal asthma medication budesonide has been shown to reduce the chance of more severe disease if taken early). Loading Outside the frenzied focus of a pandemic, new drugs face a similarly slow path to development as vaccines do. Robots have been screening millions of chemical compounds since early 2020 to find the best COVID-fighting potential, but even then thats just in a lab. And when you do find something, most will fail in people or have [bad side effects], Kelleher says. But he notes respiratory viruses are notoriously difficult to make anti-virals and other treatments for, trickier than, say, making antibiotics to fight bacteria. Even [the influenza antiviral] Tamiflu only reduces the severity of the flu by a couple of days. Tong says treatment development for COVID would benefit from more focus and funding. We need a pipeline to get therapies into clinical trials earlier and in a more co-ordinated way. He points to the example of the failed plasma trials. In the US, in particular, hundreds of thousands of people have had it, often on compassionate grounds [not just in trials] and with great expense, and now all the evidence says it doesnt seem to work. If those trials had been bigger earlier, we would have known sooner. Kelleher agrees that the worlds focus on vaccine development is crucial, but treatments for COVID are urgently needed, too. For those people where the virus has got around the vaccine or their bodies havent generated the antibodies as wed hoped, this is where you save them.