This week in Covid-19 research. Four must-know studies.
From Omicron BA.2 insights to major therapeutic trials, it was a big week.
Note: I recently asked my followers on Instagram (follow me there!) whether they wanted one deep dive on a recent Covid-19 study, or a series of “quick hits” about a few of them. The poll was conclusive. Around 80% wanted quick hits. So, today’s Inside Medicine is a summary of four important Covid-19 studies from this week. If you like this format, I can do it more often. This would be in the tradition of Brief19, the daily newsletter I edited from March 2020-June 2021.
Please let me know what you think!
This week (ending April 3, 2022), was a biggie for Covid-19 research. Here’s what you need to know from four of them.
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“Cross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2,” and “Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine,” biorxiv preprint server.
The studies: Given that there are two new versions of Omicron circulating, researchers wanted to know whether a recent infection with original Omicron (BA.1) provided protection against the newer ones (BA.2 and BA.3) as well as an older non-Omicron strain isolated back in January of 2020. Additionally, they wanted to know whether people who had recently been received a Pfizer-BioNTech booster would be protected. These were laboratory studies in which scientists measured how much blood from various patients was needed to neutralize the different forms of SARS-CoV-2. So while they imply real-world effects, these are not data from clinical studies on people.
Outcomes and commentary: Not surprisingly, a recent "original" Omicron infection (BA.1) neutralized BA.1 virus nicely. That means that repeat infections against the same version of the virus are unlikely in the short term, which is no surprise. In addition, blood from BA.1-recovered patients also neutralized the newer versions of Omicron (BA.2 and BA.3), albeit around 4-times less. But these findings are enough to imply that surviving BA.1 means that BA.2 and BA.3 infections are less likely, at least for some period (we do not know how long). Finally, neutralization of the 2020 strain with blood from Omicron survivors was detected, but the effects were markedly lower. Again, not surprising given how different the strains are.
In the second study, blood from participants who had received a 3rd dose of Pfizer a month prior neutralized all 3 forms of Omicron quite well, albeit markedly less than it neutralized the 2020 strain (3.6 to 6.4-fold less, to be precise). These effects likely wane, however, meaning that vaccines are unlikely to provide forcefield levels of protection against infection a few months after the most recent dose, though clearly some of that protection persists. However, vaccine-derived protection against long-term and severe consequences is likely to remain intact in the face of all forms of Omicron, which we have known since around two weeks after the existence of Omicron was first announced. (Go science!)
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“Early Outpatient Treatment for Covid-19 with Convalescent Plasma,” New England Journal of Medicine.
The study: outpatients who tested positive for Covid-19 were recruited and randomized to receive either convalescent plasma (blood transfusions) from patients who had recovered from Covid-19 or control plasma from non-previously infected donors.
The outcome: Those who received convalescent plasma were eventually hospitalized 2.9% of the time, compared to 6.3% among the control group. This 3.4% difference means that for every 29 people given convalescent plasma, one hospitalization was prevented.
Commentary: Out of 1,181 patients in the study, 54 (4.6%) were hospitalized. But only one vaccinated person was hospitalized, and even that individual was partially vaccinated. That means 0% (0 out of 149) fully vaccinated participants were hospitalized, 1.7% (1 out of 58), and 5.4% of unvaccinated participants were hospitalized (53 out of 974). So to me, the strongest message this trial delivers is a known one: vaccination works. But limiting the analysis to the unvaccinated is also informative because it indicates that convalescent plasma isn’t a lost cause. Earlier in the pandemic, plasma was floated as a “game changer” by some, even though major trials had failed to show a benefit. But one major previous trial was successful at least in older subgroups treated quickly, and it appears that this new one built on lessons from it and others. It seems that two factors may be contributing to plasma wins. First, it appears that using only highly concentrated donor plasma is important. In the old days, donors gave what they had, and this was transfused. Now, researchers have learned that only transfusing highly concentrated plasma is worthwhile. In a sense, we are finally learning to correctly “dose” these plasma transfusions. The other lesson is that early treatment is better, at least for plasma. While supporters of other potential therapies which have failed in rigorous trials often haplessly use the excuse that “the treatment was not given soon enough,” in this case it might be true. That said, this is both a feature and a bug. Coordinating these transfusions is complicated. A 3.4% difference in a highly motivated trial setting likely translates to a fraction of that in real life. But for places without adequate vaccine coverage (or for circumstances in which a breakthrough variant renders them powerless), plasma may turn out to be a reasonable back-up plan.
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“Effect of Early Treatment with Ivermectin among Patients with Covid-19,” New England Journal of Medicine.
Ivermectin. Here we go.
The study: Over 3,500 patients in Brazil with at least one risk factor for a poor Covid-19 outcome and within 7 days of the onset of symptoms were randomized to receive ivermectin (an anti-parasitic drug that has become the darling of Covid-19 grifters), placebo, or some other treatment.
The outcome: Ivermectin didn’t work. Regardless of whether the patients received ivermectin or not, around 1 in 6 patients required either hospitalization or an extended admission to an observation unit. The researchers also looked at other outcomes, such as viral clearance (i.e. how long it took for virus levels to become undetectable), the number of days spent in the hospital, the likelihood of needing to be placed on mechanical ventilators (and the number of days spent on ventilators), and death. No improvements were found. The researchers also made sure that they were not missing anything important by looking at whether adherence or especially early treatment made a difference. When they analyzed just the patients who actually took the ivermectin exactly as prescribed, no improvement was found. Similarly, patients who received ivermectin in the first 3 days of symptoms also did no better.
Commentary: If ivermectin works against Covid-19 at all, the effect is not large. This study certainly showed no effect. Nevertheless, as soon as the data from this study were released, ivermectin worshippers set out to undermine the findings. But unlike with convalescent plasma, the “you have to give it earlier” excuse has not worked out. The other grouse you’ll hear is that “they gave the wrong dose.” Naturally, any study that failed either gave slightly too low or slightly too high a dose (wink, wink). It’s always something.
I have two major thoughts about ivermectin. First, it likely has almost no practical effect on Covid-19. The one finding I was ever impressed by was that in a randomized trial, patients who took ivermectin seemed to gain their sense of smell back more quickly. This seems to imply that maybe ivermectin does actually do something, though unfortunately not what the grifters and zealots claim. Another fascinating recent finding worth noting is that there actually has been the hint of a mortality benefit among ivermectin recipients in trials that took place in regions with high prevalence of strongyloidiasis, a disease caused by parasitic worms, but the mortality benefit was not seen in other regions. The thought is that severe Covid-19 patients routinely receive steroids, which are known to improve outcomes, but which can actually worsen parasitic diseases like strongyloidiasis. So, it may be that ivermectin indeed has a use in treating undiagnosed worms in some Covid-19 patients. But we knew that.
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