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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 I’d 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 there’s 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 don’t work at their original jobs.
Your immune system, understandably, is not thrilled about this. While it takes a little while for it to notice you’ve 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.
How can things go wrong?
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. It’s 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, there’s 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 can’t 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. That’s 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 it’s working normally, it’s 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 we’re in the moderate or severe stages, we want to suppress the immune system to stop the cytokine storm. We don’t want to completely kill the immune system, but reducing its response significantly would lessen many of the most dangerous symptoms. In conjunction, we’d 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 isn’t 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 doesn’t 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. There’s also not that much of it to go around.
Ideally, we’d find a more easily delivered and effective antiviral product. We’re still looking.
Hydroxychloroquine is the option that’s 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 doesn’t 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 doesn’t 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 aren’t 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 don’t 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 Magazine’s 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?
There’s still a lot we don’t 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. It’s incredibly expensive, in the thousands to tens of thousands of dollars to administer. It does really wreck a person’s immune system for a while, putting them at risk of other infection. It’s something that we’d 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. It’s 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 shouldn’t take it, because it’d 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, it’s also a proof of concept. Yes, we can save a third of deaths among severe cases, but now we’ll try other immune-suppressing drugs with different doses to try to treat the cytokine storm most effectively. We’ll 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 they’ve done well with it — reducing mortality by a third is no small feat — it’s easy to see that more improvements are just around the corner.
One common refrain I’ve heard from people who have shown a lack of care about the virus was “Well, I’m going to get it at some point, it might as well be now.” But the truth is simple: it’s much better to be a coronavirus patient in June than March. That’s 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 firstname.lastname@example.org or on Twitter at @andyblarsen.