We’re a year into the coronavirus pandemic, so the math that undergirds its risks should by now be familiar. We all should know, for example, that the ability of the virus to spread depends on it being able to find a host, someone who is not protected against infection. If you have a group of 10 people, one of whom is infected and nine of whom are immune to the virus, it’s not going to be able to spread anywhere.
That calculus is well known, but there is still some uncertainty at play. To achieve herd immunity — the state where the population of immune people is dense enough to stamp out new infections — how many people need to be protected against the virus? And how good is natural immunity, resistance to infection built through exposure to the virus and contracting covid-19, the disease it causes?
The safe way to increase the number of immune people, thereby probably protecting everyone by limiting the ability of the virus to spread, is through vaccination. More vaccinated people means fewer new infections and fewer infections needed to get close to herd immunity. The closer we get to herd immunity, the safer people are who can’t get vaccinated, such as young children (at least for now).
The challenge the world faces is that the rollout of vaccines has been slow, relatively speaking. The coronavirus vaccines were developed at a lightning pace, but many parts of the world are still waiting for supplies sufficient to broadly immunize their populations. In the United States, the challenge is different: About a quarter of adult Americans say they aren’t planning on getting vaccinated against the virus, according to Economist-YouGov polling released last week.
That’s problematic in part because it means we’re less likely to get to herd immunity without millions more Americans becoming infected. Again, it’s not clear how effective natural immunity will be over the long term as new variants of the virus emerge. So we might continue to see tens of thousands of new infections each day, keeping the population at risk broadly by delaying herd immunity and continuing to add to the pandemic’s death toll in this country.
But we also see from the Economist-YouGov poll the same thing we saw in Gallup polling earlier this month: The people who are least interested in being vaccinated are also the people who are least likely to be concerned about the virus and to take other steps aimed at preventing it from spreading.
In the Economist-YouGov poll, nearly three-quarters of those who say they don’t plan on being vaccinated when they’re eligible also say they’re not too or not at all worried about the virus.
That makes some perverse sense: If you don’t see the virus as a risk, you won’t see the need to get vaccinated. Unfortunately, it also means you’re going to be less likely to do things like wear a mask in public.
Or you might be more likely to view as unnecessary precautions such as avoiding close-quarter contact with friends and family or traveling out of state.
About a quarter of adults hold the view that they won’t be vaccinated when eligible. That’s equivalent to about 64 million Americans.
Who are they? As prior polls have shown, they’re disproportionately political conservatives. At the outset of the pandemic, there was concern that vaccine skepticism would heavily be centered in non-White populations. At the moment, though, the rate of skepticism among those who say they voted for Donald Trump in 2020 and among Republicans is substantially higher than skepticism overall.
That shows up in another way in the Economist poll. Respondents were asked whose medical advice they trusted. Among those who say they don’t plan to get the vaccine, half say they trust Trump’s advice a lot or somewhat — far more than the advice of the Centers for Disease Control and Prevention or the country’s top infectious-disease expert Anthony S. Fauci.
If we look only at Republican skeptics, the difference is much larger: Half of Republican skeptics say they have a lot of trust in Trump’s medical advice.
The irony, of course, is that Trump sees the vaccine as his positive legacy on the pandemic. He’s eager to seize credit for vaccine development and has — sporadically — advocated for Americans to get the vaccine. (He got it himself while still president, without advertising that fact.) It’s his supporters, though, who are most hostile to the idea.
Trump bears most of the responsibility for that, too. Over the course of 2020, worried about reelection, he undercut containment efforts and downplayed the danger of the virus. He undermined experts such as Fauci largely out of concern that continuing to limit economic activity would erode his main argument for his reelection. Over and over, he insisted that the virus was going away without the vaccine, that it was not terribly dangerous and that America should just go about its business as usual — and his supporters heard that message.
They’re still listening to it, as the Economist poll shows. One result may be that the United States doesn’t reach herd immunity through vaccinations and, instead, some large chunk of those tens of millions of skeptics end up being exposed to the virus. Some of them will die. Some may risk repeat infections from new variants against which a vaccine offers better protection. Some of those unable to get vaccinated may also become sick from the virus because we haven’t achieved herd immunity, suffering long-term complications from covid-19.
Trump wants his legacy to be the rollout of the vaccine. His legacy will also probably include fostering skepticism about the vaccine that limits its utility in containing the pandemic.
But some find science-by-press-release troubling.
Anti-inflammatory oral drug colchicine improved COVID-19 outcomes for patients with relatively mild cases, according to certain topline results from the COLCORONA trial announced in a brief press release.
Overall, the drug used for gout and rheumatic diseases reduced risk of death or hospitalizations by 21% versus placebo, which “approached statistical significance.”
However, there was a significant effect among the 4,159 of 4,488 patients who had their diagnosis of COVID-19 confirmed by a positive PCR test:
- 25% fewer hospitalizations
- 50% less need for mechanical ventilation
- 44% fewer deaths
If full data confirm the topline claims — the press release offered no other details, and did not mention plans for publication or conference presentation — colchicine would become the first oral drug proven to benefit non-hospitalized patients with COVID-19.
“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” principal investigator Jean-Claude Tardif, MD, of the Montreal Heart Institute, said in the press release. He predicted its use “could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.”
Currently, the “tiny list of outpatient therapies that work” for COVID-19 includes convalescent plasma and monoclonal antibodies, which “are logistically challenging (require infusions, must be started very early after symptom onset),” tweeted Ilan Schwartz, MD, PhD, an infectious diseases researcher at the University of Alberta in Edmonton.
The COLCORONA findings were “very encouraging,” tweeted Martin Landray, MB ChB, PhD, of the Big Data Institute at the University of Oxford in England. His group’s RECOVERY trial has already randomized more than 6,500 hospitalized patients to colchicine versus usual care as one of the arms of the platform trial, though he did not offer any findings from that study.
“Different stage of disease so remains an important question,” he tweeted. “Maybe old drugs can learn new tricks!” Landray added, pointing to dexamethasone.
A small open-label, randomized trial from Greece had also shown less clinical status deterioration in hospitalized patients on colchicine.
“I think this is an exciting time. Many groups have been pursuing lots of different questions related to COVID and its complications,” commented Richard Kovacs, MD, immediate past-president of the American College of Cardiology. “We’re now beginning to see the fruit of those studies.”
The COLCORONA announcement came late Friday, following closely on the heels of the topline results from the ACTIVE-4a, REMAP-CAP, and ATTACC trials showing a significant morbidity and mortality advantage to therapeutic-dose anticoagulation in non-ICU patients in the hospital for COVID-19.
COLCORONA was conducted remotely, without in-person contact, with participants across Canada, the U.S., Europe, South America, and South Africa. It randomized participants double-blind to colchicine 0.5 mg or a matching placebo twice daily for the first 3 days and then once daily for the last 27 days.
Participants were ages 40 and older, not hospitalized at the time of enrollment, and had at least one risk factor for COVID-19 complications: age 70-plus, obesity, diabetes, uncontrolled hypertension, known asthma or chronic obstructive pulmonary disease, known heart failure, known coronary disease, fever of ≥38.4°C (101.12°F) within the last 48 hours, dyspnea at presentation, or certain blood cell abnormalities.
It had been planned as a 6,000-patient trial, but whether it was stopped for efficacy at a preplanned interim analysis or for some other reason was not spelled out in the press release. Whether the PCR-positive subgroup was preplanned also wasn’t clear. Key details such as confidence intervals, adverse effects, and subgroup results were omitted as well.
While a full manuscript is reportedly underway, “we don’t know enough to bring this into practice yet,” argued Kovacs.
Some physicians also warned about the potential for misuse of the findings and attendant risks.
Dhruv Nayyar, MD, of the University of Toronto, tweeted that he has already had “patients inquiring why we are not starting colchicine for them. Science by press release puts us in a difficult position while providing care. I just want to see the data.”
Angela Rasmussen, MD, a virologist with the Georgetown Center for Global Health Science and Security’s Viral Emergence Research Initiative in Washington, agreed, tweeting: “When HCQ [hydroxychloroquine] was promoted without solid data, there was at least one death from an overdose. We don’t need people self-medicating with colchicine.”
As was the case with hydroxychloroquine before the papers proved little efficacy in COVID-19, Kovacs told MedPage Today: “We always get concerned when these drugs are repurposed that we might see an unintended run on the drug and lessen the supply.”
Citing the well-known diarrheal side effect of colchicine, infectious diseases specialist Edsel Salvana, MD, of the University of Pittsburgh and University of the Philippines in Manila, tweeted a plea for use only in the trial-proven patient population with confirmed COVID-19 — not prophylaxis.
The dose used was on par with that used in cardiovascular prevention and other indications, so the diarrhea incidence would probably follow the roughly 10% rate seen in the COLCOT trial, Kovacs suggested.
In the clinic, too, there are some cautions. As Elin Roddy, MD, a respiratory physician at Shrewsbury and Telford Hospital NHS Trust in England, tweeted: “Lots of drug interactions with colchicine potentially — statins, macrolides, diltiazem — we have literally been running up to the ward to cross off clarithromycin if RECOVERY randomises to colchicine.”