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Despite my best intentions to not fearmonger, I have to admit: My last piece on the long-term consequences of catching COVID-19 was, well, frightening.

So in an effort to balance that out, I think it’s time to focus on some good news happening in the coronavirus field, which we’ll explore in a series of articles over the next couple of weeks. The truth is that we’re making undeniable progress in our understanding of the disease, and while that progress is gradual, it’s still worth highlighting.

To be clear, I’m not going to cherry-pick only the good news — this won’t be slanted, I’ll include the bad too. And I think it’s important to note that the fact we’re understanding the virus more and more isn’t inconsistent with the number of cases and deaths growing. That we’re making strides in understanding the virus is, if anything, a reason to continue to engage in precautions. It’s a lot easier to commit to wearing a mask when the end may be in sight.

So with that, we’ll return to what I’ve previously called The Most Important Topic In The World: Vaccines.

Progress with Pfizer

At the start of the pandemic, vaccine candidates from Pfizer — the “P” is silent, which ruins my attempt at alliteration in the title of this section — weren’t necessarily at the front of the race. But developments in recent weeks have made it clear that those scientists have been working hard, and their vaccine candidates have real potential.

They began by teaming up with Germany-based BioNTech, a smaller company with experience in working with RNA vaccines. It was an extension of a partnership they started in 2018 focused on the flu, but when it became clear in mid-March that a worldwide vaccine for coronavirus would be needed, the companies agreed to work on that, too. They started on four vaccine candidates.

This month, they released data from a combined Phase I/II study on the safety and efficacy of one of their vaccines. Remember, these are small trials primarily designed to see whether the vaccine is safe and to hint at effectiveness. Large trials are still needed.

In all, 12 patients got 10 microgram doses on the first and 21st day of the study, 12 patients got 30 microgram doses at those same intervals, and 12 got a single 100 microgram dose at the start. Nine people got a placebo.

After injecting this vaccine, there were some side effects. Reports of mild to moderate fatigue and headaches happened in all groups (including the placebo), but more frequently in the bigger doses. After the second shot, one person in the small-dose group got a fever, while seven people in the middle group got a fever — nearly all of which resolved in one day. They decided not to give a second shot to the big-dose group due to these reactions.

These kinds of side effects aren’t uncommon in flu vaccines, though obviously you want to minimize them. One study found one-day flu-like symptoms happened in about 1 in 7 people who got the flu vaccine.

But the Pfizer vaccine clearly worked.

They compared how many antibodies each dosing group had to a group of people who had recovered from the coronavirus. After the first injection, those in the small-dose group had nearly double the number of antibodies as those who had recovered from the disease. The middle-dose group had nearly triple. And after that second dose, the small-dose group had eight times the antibodies, while the middle-dose group had 50 times the antibodies. That’s a lot of antibodies!

It’s extremely promising, though, that the vaccine worked even in the smallest-dose group and even after only one shot. They’re going to move forward with the Phase III trial involving tens of thousands of people with the smaller doses, and think that by September, they’ll have enough data to submit to the FDA, which might give “potential approval in October, if we are lucky,” according to Pfizer’s CEO in Time. On Monday, Pfizer announced that it had received FDA fast-track status on this vaccine candidate, plus a closely related one.

Onward with Oxford

That progress moves Pfizer closer to Oxford, the leader in the vaccine race. Oxford is now undergoing Phase III trials in Brazil, South Africa and the United Kingdom. The United States is expected to be added in August with patients in 33 sites around the nation.

While Pfizer says it could receive FDA approval in October, Oxford’s effort — buoyed by support from AstraZeneca — believes it could have results from the trials by the end of August and be ready to deliver some of the vaccine in September, with perhaps the start of widespread distribution in October.

AstraZeneca is already starting to produce the vaccine, even before Phase III trials are completed. The company recently committed to creating 2 billion doses, including 400 million by the end of 2020.

You may remember the Oxford vaccine from my last recap: It had promising results in humans, but when monkeys were given huge doses of the virus, it prevented disease severity but didn’t totally stop infections. Phase III is the stage designed to test effectiveness to the highest degree, so we’ll know soon enough whether or not this vaccine works well.

Merit and mishaps from Moderna

On Tuesday afternoon, Moderna finally published the results of the first Phase I trial that got us all excited in May about their RNA vaccine. Back then, they had only a news release, but now we have the results published in the New England Journal of Medicine. The study backs up the hype, though we should note that, unlike Pfizer’s vaccine, the antibody levels generated were only higher than recovered patients after people received a second booster shot.

“The hallmark of a vaccine is one that can actually mimic natural infection and induce the kind of response that you would get with natural infection. And it looks like, at least in this limited, small number of individuals, that is exactly what’s happening,” Dr. Anthony Fauci told STAT News about the trial. “The data really look quite good, and there were no serious adverse events.”

The downside is that the vaccine has had some discouraging hiccups in timing. The big one is the delay in their Phase III trial, which was supposed to start on July 9, but on Tuesday, the company announced it will start July 27. I don’t need to tell you that every week matters here, so a delay isn’t great.

The delay is due to changes to the trial plan, the details of which were partially explained in a University of Colorado article, where 1,000 of the 30,000 patients nationwide will come from. They’ll be recruited from a variety of patients and hospital staff, and people at high risk will be among the tested population.

Trial participants will be followed for two years after they get the injection, but that doesn’t mean that we have to wait two years for results: if preliminary data is good enough, Moderna will ask for and likely receive an FDA emergency authorization to give it out sooner.

The Colorado doctor quoted in the article says that would mean widespread vaccination in the American public “by next spring.” Essentially, Moderna’s production and distribution capabilities may not be as good as the ones from the Big Pharma companies, though Moderna has tied up deals to make 100 million vials, beginning production in the third quarter.

Overall, Moderna still represents a promising candidate, and it is still ahead of Pfizer’s RNA vaccine in terms of beginning the Phase III trial.

Continuing in China

News from China about its vaccine progress makes fewer waves in the Western world, but still represents progress in our battle to understand what’s going on. I understand why people are hesitant to accept Chinese results, but the truth is their research into the virus has been some of the world’s best since the end of January.

First, Sinovac reported positive results from its inactivated vaccine in Phase I/II trials in mid-June. Inactivated vaccines are some of the simplest forms of vaccine: you just take some of the virus, kill it with heat and/or chemicals, and then inject that. Then, the body recognizes the infection and hopefully creates antibodies. Because the virus is dead, the body tends to create a weaker immune response than it does for other kinds of vaccines, so that’s something to watch for. Still, having multiple ways to attack this problem is potentially really valuable.

China’s government leaders did something pretty out there with another vaccine candidate. Cansino’s Ad5-nCoV, which is a DNA vaccine pretty similar to Oxford’s effort, worked well in Phase I/II trials. So they approved its use in the Chinese military. That country is essentially using the military as an arm of the Phase III research. It’s a defensible but questionable decision, and something that wouldn’t fly in America.

I don’t think America would help produce and distribute a Chinese vaccine, but other nations plan to. Brazil, for example, entered an agreement with Sinovac to distribute millions of doses.

Nifty notes

Some other positives from the world of vaccines:

• One thing doctors were a little worried about is something called antibody-dependent enhancement (ADE) of these vaccines. You see, in some disease/vaccine combinations, antibodies can be created that attach to the virus that actually help the virus multiply, not stop it. It’s something we’ve seen in dengue fever research, as well as a small percentage of humans with RSV. So scientists have been on high alert for any enhancement happening in any of these vaccine trials.

The good news: we’ve seen no ADE. We haven’t seen it in any of the human trials so far, across thousands of combined participants. And when we gave one promising vaccine to mice, we didn’t see any ADE either. Of course, it’s something to watch for when we start giving vaccines to tens of thousands of people in Phase III trials, but so far, so good.

• Another concern was whether vaccines would work only against certain strains of the virus. Remember, there was one strain found in Asia and most of the early spread in the western United States, and another in Europe and the rest of the U.S.

But a recent study found that antibodies created by sickness of one variant are just as effective in preventing infection of the other variant. That’s what most scientists expected, but still, it’s good to confirm. Our vaccines under development that pass trials will likely work against everything that’s currently spreading.

• Some of the early talk about vaccine trials centered on challenge testing: giving people a vaccine candidate, and then literally expose them to the virus to see if the vaccine works. Usually, this is unethical, but in a worldwide pandemic, it was something we were considering. Over 30,000 people signed up to be challenge tested on one website.

But with outbreaks reaching high numbers of people in various locations, like Brazil, India, Arizona, and Florida, there’s just no real need to break that ethical line. Instead, we can just give the vaccine to people in those places and see if they catch it in their everyday lives. Obviously, it’s terrible that we’re in such a position, but not needing challenge testing is the silver lining.