StemCell Therapy

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It is better to be a coronavirus patient in June than it was in March.

Back then, there was just so little we knew about the virus: after all, it was a brand new thing. But as scientists and doctors battle this disease that has infected millions and killed more than 460,000 people around the globe, they have learned a good deal about how it attacks the body, and a little more about how to treat it. That means a better chance of survival for those who have the disease.

Unfortunately, this is relevant for an ever-increasing number of Utahns, with more people getting the virus and more people hospitalized than ever before. With that in mind, I thought Id walk you through what we know about the coronavirus right now, as jargon free as possible.

What happens when you inhale the coronavirus, anyway?

Naturally, the virus finds itself in your lungs. Once there, the virus bumps around the inner walls until it finds a cell it can connect to it turns out the spiky exterior on coronaviruses is really well suited to connecting to lung cells called alveolar cells, which are the ones that bring oxygen to your blood. The average person has about 480 million alveoli per lung, so theres plenty of opportunity for infection.

The virus injects its genetic code into the cell, hijacking it and turning it into a copy machine. That produces more of the virus, which can infect your own cells and be exhaled to infect others. As more and more cells become infected, they dont work at their original jobs.

Your immune system, understandably, is not thrilled about this. While it takes a little while for it to notice youve been infected and do something about it anywhere from 2-14 days, with an average of 4-5 days it does eventually mount a response that causes many of the coronavirus symptoms, such as fever or cough. That immune response also typically works to cure people: it kills the infected copy machine cells, your body naturally creates new working ones in their place, and you recover.

Normally, the immune system is pretty good about starting up and shutting down at the right times using an in-body signaling system made up of cytokines. Cytokines promote all sorts of useful immune system functions, but one is that they send more repairing blood to infected sites. They even make blood vessels more permeable than usual so immune system cells can more efficiently get from the blood to attack the infected cells.

However, sometimes the immune system gets overexuberant, as one medical education site put it. Its not always clear why, but in certain cases very bad infections, burns, or other trauma the immune system ends up producing and sending way too many cytokines. This is called a cytokine storm.

The cytokine storm in COVID-19 cases cause big problems. For one, theres now way too much blood going to these infected sites, and they get super inflamed. All of the fluid and blood everywhere means that even the uninfected alveolar cells in your lungs are drowned, and cant work to bring oxygen in your body anymore. That causes Acute Respiratory Distress Syndrome (ARDS).

And those previously-helpful permeable blood vessels now become too permeable: they spring leaks. That means the blood clot system has to start working to fix those leaks, but that creates little blood clots all around your body.

At least the majority of people who die or experience severe symptoms due to COVID-19 end up facing ARDS, either due to the initial viral cell killing or the cytokine storm. But others die from or also experience the results of those blood clots, with problems like heart or kidney failure, even strokes. Thats one reason we kept seeing all of these COVID-19 patients with unexpected symptoms: once your circulatory system stops working well, all sorts of weird stuff can happen.

A team of Harvard researchers proposed a three stage categorization system for coronavirus patients. Stage 1 is mild coronavirus, caused mostly by the negative effects of the virus itself. But the biggest problems come in Stage 3, when the immune system is essentially attacking the body.

What does this mean for treating the virus?

It means that we have to use different treatments at different stages.

Essentially, at the beginning, we want to help the immune system as much as possible. When its working normally, its terrific; so terrific that the majority of people face only mild symptoms. We also want to prevent the virus from making copy machines of itself using antiviral drugs.

However, once were in the moderate or severe stages, we want to suppress the immune system to stop the cytokine storm. We dont want to completely kill the immune system, but reducing its response significantly would lessen many of the most dangerous symptoms. In conjunction, wed also like to prevent or mitigate the effects of those micro blood clots.

It is a tricky balance. In one stage, we want to help the immune system, and in later stages, we want to suppress it. And diagnosing whether a cytokine storm is about to occur or is currently underway isnt necessarily an immediate process: there are lab tests to perform.

Still, this split approach looks like our best chance of treating COVID-19 patients.

What treatments are there for the early stages of the disease?

Remdesivir is the most well-tested antiviral product we have to use against COVID-19. It works by inhibiting virus production in those infected, copy machine cells, and in a randomized, controlled trial, it made a statistically significant but relatively small impact on the amount of time people spent in the hospital with the virus: 11 days on average instead of 14.

It just doesnt make sense to give to everyone with mild symptoms: remdesivir has to be delivered intravenously, which means it probably has to be done in a hospital. Theres also not that much of it to go around.

Ideally, wed find a more easily delivered and effective antiviral product. Were still looking.

Hydroxychloroquine is the option thats gotten the most attention, in part for political reasons. The thinking here is that it works to help prevent malaria infections, so it might work with the coronavirus. By one count, 158 studies that tried to find out whether hydroxychloroquine works or not, in all sorts of combinations. Most of them have been poorly designed, or too small to be elucidating, or based on data so flawed they had to be retracted.

Based on a majority of the studies, the most likely scenario is that it doesnt work against this virus. There are those who will say that it needs to be tested with azithromycin and/or zinc, or only in pre-symptomatic patients, or only on Thursdays. But the scientific community is moving away from this one. The FDA recently pulled its emergency approval to use the drug to treat COVID-19 and the World Health Organization dropped the drug from its huge study into coronavirus treatments.

Another promising path is the use of antibodies. This study from the University of Washington looked at how injecting someone with blood plasma from recovered COVID-19 patients which contains antibodies specific to the coronavirus actually prevented the virus from infecting cells in the first place. We also know that injecting plasma into hospitalized people seems to make a big difference, unless we inject it too late, in which case it probably doesnt work. In short, the antibodies help with the virus but not with the cytokine storm.

The traditional problem with the plasma antibody strategy is that you need the blood of someone who already had the disease but recently recovered, and there arent that many doses of it to go around. Furthermore, those doses tend to vary wildly in terms of effectiveness, because different people produce different numbers and types of antibodies. Finally, the antibodies dont last forever, probably only a month or two.

But if we create those antibodies in a lab, we should be able to make enough doses to give to people who need protection. You can imagine those antibody injections being the bridge to a vaccine, administered to healthcare workers, those in long-term care facilities, or anyone else exposed to an outbreak, with or without symptoms. Science Magazines Derek Lowe had a good roundup of the companies working to create and test these antibodies; some think those treatments will be available by the fall.

What treatments are there for the late stages of the disease?

Theres still a lot we dont know about the cytokine storm, but we do have some pretty good ways of slowing down the immune system. Obviously, we want to test these in the context of COVID-19.

The first one that showed significant results in a big study was tocilizumab. When given to patients in Stage 2, it reduced intensive care unit admission by more than half and significantly cut mortality as well.

It has problems though. Its incredibly expensive, in the thousands to tens of thousands of dollars to administer. It does really wreck a persons immune system for a while, putting them at risk of other infection. Its something that wed want to give to save lives, but probably not in large numbers.

Luckily, we found a much better solution. Dexamethasone is a cheap and widely available steroid that cut deaths by one-third in a study released this week of 2,100 participants in the UK with severe COVID-19. Its a pill. It costs about $6 per day.

You can see why the head scientist in the study called it a major breakthrough.

Now remember: this is an immune system suppressant. People with Stage 1 coronavirus definitely shouldnt take it, because itd be handicapping the very thing they need most. But those in later stages might find it effective in weathering the cytokine storm.

Just like with remdesivir, its also a proof of concept. Yes, we can save a third of deaths among severe cases, but now well try other immune-suppressing drugs with different doses to try to treat the cytokine storm most effectively. Well get better at it over time.

That will be the continuation of a positive coronavirus trend: a lowering in the fatality rate. One study looked at the rate of deaths of people in Italy and found a reduction in fatality rate from 10.8% to 6% from March to April. Testing differences make this issue difficult to study, but it really does appear that doctors have gotten better at treating the disease.

That was another reason all of us have taken so many coronavirus precautions: to buy doctors time. While theyve done well with it reducing mortality by a third is no small feat its easy to see that more improvements are just around the corner.

One common refrain Ive heard from people who have shown a lack of care about the virus was Well, Im going to get it at some point, it might as well be now. But the truth is simple: its much better to be a coronavirus patient in June than March. Thats a trend I expect to continue moving forward.

Andy Larsen is a Tribune sports reporter who covers the Utah Jazz. During this crisis, he has been assigned to dig into the numbers surrounding the coronavirus. You can reach Andy at alarsen@sltrib.com or on Twitter at @andyblarsen.

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Coronavirus treatments are improving. Here's a guide to what works and why. - Salt Lake Tribune

This entry was posted on June 22, 2020 at 5:43 am and is filed under Immune System. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |