Disease experts warn we're not free of COVID-19: 'The world needs a reality check'

Maria Van Kerkhove, a World Health Organization epidemiologist, was in her Geneva office last weekend preparing for a keynote address when a simple phrase came to mind. She had been pondering the dismaying rise in coronavirus infections globally during the previous three weeks, reversing promising trends of late spring. The surge came as people across much of the Northern Hemisphere were moving around again in a suddenly freewheeling summer - as if the pandemic were over.

She wrote in her notebook: "The world needs a reality check."

Van Kerkhove's subsequent comments on Twitter pointing out the lack of social distancing drew predictable flak from the social media trolls, something she has gotten used to in the past year and a half. But she is not an outlier. Around the world, scientists and public health officials fear that the world's protracted battle against the coronavirus is at a delicate and dangerous moment.

Reality checks abound. Coronavirus infections are surging in places with low vaccination rates. SARS-CoV-2 is continuing to mutate. Researchers have confirmed the delta variant is far more transmissible than earlier strains. Although the vaccines remain remarkably effective, the virus has bountiful opportunities to find new ways to evade immunity. Most of the world remains unvaccinated.

And so the end of the pandemic remains somewhere over the horizon.

"We're getting further away from the end than we should be. We're in a bad place right now globally," Van Kerkhove said.

Similarly dismayed is Francis S. Collins, director of the National Institutes of Health. Last summer, he watched cases in the United States spike, particularly in the Sun Belt, after what he felt was a premature end to spring restrictions. This summer, he is not surprised by the rise in infections across a country where many people haven't gotten their shots and have returned to pre-pandemic behavior.

"It's like we've been to this movie several times in the last year and half, and it doesn't end well. Somehow, we're running the tape again. It's all predictable," Collins said.

Coronavirus infections in the United States rose nearly 70% in a single week, officials reported Friday, and hospitalizations and deaths rose 36% and 26%, respectively. Almost every state has experienced a rise in cases. Florida, populous and not highly vaccinated, is seeing a surge in cases. In hotspots such as Arkansas and Missouri, COVID wards are opening up again in hospitals.

Los Angeles County this past week announced that it had to reinstate indoor mask requirements for everyone, regardless of vaccination status. Breakthrough infections among vaccinated people provide another reality check. Thursday night's prime-time baseball game between the New York Yankees and Boston Red Sox was canceled when six Yankees players - most of them vaccinated - tested positive for the virus.

Many breakthrough infections will produce no symptoms. The Centers for Disease Control and Prevention decided in May to track only breakthrough infections leading to hospitalization.

The vaccines, though marvels of basic and applied science, do not form an impenetrable shield against SARS-CoV-2. They work as advertised, meaning they usually prevent severe illness and death, but they do not deliver what is known as "sterilizing immunity."

The CDC issued a statement Friday saying the agency has multiple programs, working with state and local partners, to track vaccine effectiveness.

"COVID-19 vaccines are effective and are a critical tool to help bring the pandemic under control. However, no vaccines are 100% effective at preventing illness in vaccinated people. There will be a small percentage of fully vaccinated people who still get sick, be hospitalized, or die from COVID-19. As with other vaccines, this is expected. As the number of people who are vaccinated goes up, the number of breakthrough cases is also expected to increase," the CDC said.

The next reality check comes from the virus itself. The delta variant has mutations that significantly enhance transmissibility, and it is responsible for a majority of new infections in the United States as it outcompetes other strains. Mutations in the virus are inevitable and complicate forecasts of how the pandemic will play out. The world is in the midst of a global experiment in which a single virus is turning into a full Greek alphabet of distinct strains, each with its own suite of mutations.

"They're evolving. Even the delta variant, we have two sublineages we are monitoring," Van Kerkhove said. "Everyone is fixated on the delta, but we should be prepared for more."

Amid these concerns are positive signs of long-term progress against COVID-19, the illness caused by the virus. That's a reality check on the positive side of the ledger. This isn't 2020. The increase in hospitalizations has been less dramatic than the increase in reported infections. That's because the vaccines - a tool the world lacked a year ago - usually prevent severe illness.

"The game changer is if and when we see large numbers of vaccinated individuals returning to hospitals. But we are not seeing that," said David Rubin, director of PolicyLab at Children's Hospital of Philadelphia.

This hints at how the pandemic may eventually play out: The virus would become endemic. It would not be eradicated - and would still cause occasional clusters of infection - but it would not ignite runaway outbreaks nor be nearly as lethal as when it emerged into the human population. That drop in lethality will be driven less by changes in the virus itself than by the changed immunological landscape.

For people with at least partial immunity, COVID-19 could become more like influenza or even a cold, which are caused by viruses that are at least somewhat familiar to our immune systems. Four other coronaviruses are endemic in humans and are responsible for a significant fraction of colds.

This scenario - call it Scenario A - has been the general assumption or hope of many infectious-disease experts since the start of the pandemic. The dialing down of the lethality of the disease would be an example of history repeating itself: The 1918 influenza pandemic was caused by a virus that never vanished, but instead became the cause of the seasonal flu.

SARS-CoV-2 and COVID-19 are often referred to as if they were interchangeable. But the trajectory of the virus increasingly is distinct from the trajectory of the disease. As time goes on, more people will have immunity from a previous natural infection or from vaccination, and SARS-CoV-2 will pose less of a threat to them than it will to people unvaccinated or never previously infected.

"We're really teasing apart SARS-CoV-2 the virus from COVID-19, the disease," said Jennie Lavine, an Emory University researcher and lead author of a paper in Science earlier this year showing how the virus may become endemic. There won't be a single moment when the virus becomes endemic, she said. It will happen gradually, as the virus loses its virulence. In Scenario A, the pandemic as we know it comes to an end.

"That's not saying you won't get infected again, it's saying that you won't get really sick from it," she said.

Janis Orlowski, chief health-care officer of the Association of American Medical Colleges, offers one version of Scenario B: "Delta goes on to epsilon which goes on to lambda, and that becomes another ugly virus. ...The virus mutates to a strain that we are not effectively vaccinated against - and that leads us into another ugly year."

(For the record: There already is an epsilon and a lambda.)

Orlowski adds, "I think Scenario B is less likely, but is still a concern because we are not vaccinated at the rate we should be."

New scientific research, including two reports highlighted by Collins on his NIH blog, indicates that important elements of immunity appear to remain durable against the virus even when antibodies begin to wane. And although Pfizer-BioNTech - the companies behind one of the three authorized vaccines in the United States - put the idea of boosters into play with a recent news release saying people may need them six to 12 months after being fully vaccinated, many experts, including Collins, regarded the announcement as premature.

Some people who are immunocompromised - for example, from taking powerful drugs to reduce chances of organ rejection after undergoing a transplant - may need another vaccine dose in the near term, especially if tests show they have not mounted any immune response to the vaccines. But Collins doesn't consider that a "booster" so much as another attempt to get people to the initial stage of immunity.

The bigger question for public health officials is whether they can persuade millions more people to get jabbed in the arm for the first time. Roughly one-third of adults in the United States remain unvaccinated. Vaccine uptake is lowest among younger age groups that are also at lower risk of severe illness from COVID-19, but they represent a growing percentage of cases in hospitals.

Misinformation has run rampant. The vaccines are not, contrary to one rumor, "gene therapy." They do not implant microchips. They are not part of a plot. And although they can cause side-effects - and on rare occasions, dangerous ones - the vaccines have passed rigorous safety reviews.

Surgeon General Vivek H. Murthy released a report Thursday decrying the epidemic of misinformation. On Friday, he called out "technology companies" that he said enabled misinformation "to poison our information environment with little accountability to their users." President Joe Biden doubled down on that Friday as he boarded the Marine One helicopter for a trip to Camp David: "They're killing people," he said of the social media platforms that spread misinformation.

Even if, through vaccination and prudent behavior, the virus is brought under control, the rattling psychological effects of the pandemic could persist.

As Lavine points out, people have been told repeatedly for a year and a half that this virus is a potential killer. For many of those people, it will be difficult to let go of COVID-19 fears. The many unknowns about COVID-19 will make risk tolerance calculations difficult. This remains a new virus and a new disease, and scientists and doctors are still trying to understand what they're looking at.

"Nobody has had COVID for 10 years. So there's an unknown factor, and that is going to make it scary for a while because people are scared of the unknown," said David W. Dowdy, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health.

Meanwhile, many people are not scared at all, don't feel vulnerable, or simply are done - done, done, done - with the pandemic. Van Kerkhove, the WHO epidemiologist, was upset last Sunday at the sight of unmasked people across Europe crowding into bars to watch the European championship soccer match between Italy and England.

"It's really disheartening, and it's really devastating to see situations where we can facilitate spread," she said. "I want to go to those football matches, too. I want to go to the bar and have a drink. I want to go out to dinner."

But she's not ready. She knows too much.

"The situation globally is so dynamic, it's so uncertain, and is so fragile," she said.