UCSF Grand Rounds: Eric Topol damns the ‘inevitability camp’

Amidst the latest omicron surge, Dr. Eric Topol, director of the Scripps Research Translational Institute, described our current situation as a “warped view about how mild” omicron is, because it “can kill and put a lot of people in the hospital.” 

UCSF Grand Rounds Moderator Dr. Bob Wachter described Topol as the one person he would follow for covid updates if he was stuck on a deserted island. Topol said he was concerned about hospitalizations “now well over one 150,000.”  But he, too, said that there are some early signs that “we’re going to get on this descent.” 

However, Topol was especially anxious to debunk the “inevitability camp,” or the idea espoused by some (including Dr. Anthony Fauci) that almost everyone will get omicron. Some take this idea a step further, and view omicron as a replacement for getting a vaccine or booster. Topol instead said it is likely that almost everyone will be exposed to omicron, but not that everyone will get sick with it. 

“Let’s not invite an unpredictable virus. It can cause long covid,” among other negative consequences, especially for the immunocompromised, he said. “The idea of this inevitability, we want to move away from that.”

There are a few countries where the huge surge in omicron cases has begun to drop, including the United Kingdom, and Topol said that what is being observed in U.S. cities, such as New York City, potentially indicates that the decline could come in the next few weeks. However, there are many parts of the country that are “much more vulnerable than the ones that have been first exposed,” with lower vaccination rates, especially among children, which is what worries Topol in the weeks ahead.  

“Once we get through that phase sometime, hopefully in February, then we’ll have a better sense of whether we’re moving towards some containment, or is this just a lull before a second omicron wave, or yet another Greek letter variant,” he said. 

As to why omicron waves have come down so rapidly, Topol said this is a mystery, and speculations are not backed up by data at this point. The other mystery he highlighted is omicron’s “extraordinary” increased contagiousness, which he said is partly driven by immune escape, or the variant’s potential ability to evade a person’s immune response.

Given omicron’s increased transmissibility, Wachter asked if we should be reconsidering older covid practices, such as increased protection outside or wiping down our mail. Topol is “a little concerned” about outdoor transmission, and suggested wearing masks outdoors “just because we don’t know” what exactly is behind the increased transmissibility. 

Regarding rapid tests, Topol said they aren’t perfect, but that reports and data have “have all reinforced that their performance is quite reasonable.” Multiple tests are needed to be more sure, and the timing is important, he said. 

Topol was very critical of the recent guideline change from the U.S. Centers for Disease Prevention and Control. That change shortens the period that individuals who test positive for covid must isolate, from 10 days to five days if they are asymptomatic, and advises them to wear masks around others for the next five days. 

“That, to me, was one of the real low points of our CDC, unfortunately,” he said, noting that one-third of individuals will still test positive for covid after five days, according to a “very important” preprint paper. He suggested a policy that allowed for ending isolation only after an individual has two consecutive days of negative test results. 

He also bemoaned the lack of availability of rapid tests, as well as KN95 and N95 masks, to the general population, and called recent government attempts to provide all Americans with these supplies “much too late.”

“Clearly, they were leaning ‘let’s bet big on the vaccines and de-emphasize the others,” Topol said of the Biden administration. The president decided not to place a large order for Paxlovid, an oral antiviral that reduces covid hospitalizations by 90 percent, when he was approached by three large pharmaceutical companies last summer, even when they told him it would take several months to build up a large supply. 

Manufacturing the drug requires “a lot of complex steps,” and the rate of production is slowed by a limited supply of raw materials mainly from China, Topol said. Pfizer has promised 80 million treatments by the end of this year but, barring any surprises, even that is “very insufficient.” 

“They made a big bet on vaccines with Operation Warp Speed, but they weren’t willing to make other big bets,” he said. He also noted that the administration has also failed to adequately improve data systems when it comes to collecting information about hospitalizations and deaths in the United States.  

Paxlovid has been shown in studies to cause more than a 10-fold decrease in viral load, which will greatly help reduce transmission, Topol said. He also believes it will be effective against other future variants. 

Tackling another issue of uncertainty, Topol said that we have not had nearly as many answers and definitions about long covid as we need. There is some difficulty in defining the terms of long covid, but it “can be a majorly disabling chronic condition” that could affect 10 percent of people who get covid, depending on how you define the syndrome, he said. 

Long covid may pose a bigger problem with omicron, as most long cases occur with mild or moderate covid, and the variant’s higher immune escape could make it more difficult for people to get over it. Vaccines may help reduce the risk of long covid by as much as one-third or one-half, but those numbers are questionable, as there is currently no randomized trial data. 

Looking ahead, Topol is worried about the possibility of a future variant with immune escape, hindering the effectiveness of vaccines. No one predicted the viral evolution of omicron, “so we don’t know what’s in store and we have to be truth telling about that. We could see a variant that’s worse,” he said. 

For this reason, Topol believes more should be invested in creating a variant-proof vaccine, which he said would be made by reverse-engineering broad neutralizing antibodies found in less than 0.1 percent of the population that are “incredibly effective.” 

While there are academic labs exploring this possibility, and the antibodies responded well to omicron, there is not interest in the same public-private partnerships that were carried out under Operation Warp Speed, he said. “The only way you’re going to be able to tell if it’s pan-coronavirus and variant-proof is getting it out there and showing that, whatever this freaking virus shows us, we can protect against it.” 

In the meantime, some individuals are calling for a fourth shot to further prevent covid infection, especially among older populations. This policy is currently being carried out for those over 60 in Israel, and Topol is confident that the data will give us an answer about the effectiveness of such a policy in time. 

See our previous Grand Rounds coverage here.