To prevent the possible spread of disease, a portable isolation chamber is used to deliver a COVID-19 patient to the Vitebsk Regional Clinical Infection Hospital in Belarus/Serge Serebro, Wikimedia Commons

Update: This story was edited on Sept. 7, 2020 to reflect Chinese findings of T-cell immunity for SARS-CoV-2.

With COVID-19 cases at over 27 million and some residents of most of the human-occupied earth now infected, scientists have begun to contemplate what might happen if the coronavirus SARS-CoV-2 transitions from pandemic to endemic.

SARS-CoV-2 is the pathogen that manifests itself as COVID-19 if you get a big enough dose, or if your natural immune systems is not strong enough to fight off a low dose, or if you’re unlucky enough to encounter the wrong combination of infectious dose and innate immunity.

When the disease first appeared at the start of the year, almost one in 10 people diagnosed with it were dying. That number has steadily fallen but doctors aren’t sure why.

“In England, the proportion of people infected by the coronavirus who later died was certainly lower in early August than it was in late June,” New Scientist reported in late August. “Over the period, this infection fatality rate (IFR) dropped by between 55 and 80 percent, depending on which data set was used.”

Various suggestions have been offered to explain the shift, varying from improved treatment to more infections among young people unlikely to die to a weaker strain of SARS-CoV-2 becoming more prevalent in some areas.

For a coronavirus to shift from a deadly killer in the short term to a nagging problem in the long run would not be unprecedented.

“…CoV-2 is not the first coronavirus identified with human-to-human transmission,” researchers from Emory University and The Pennsylvania State University observed in a paper posted Saturday on the medRxiv website. “There are six other coronaviruses with known human chains of transmission, and these can provide clues to future scenarios for the current pandemic.

“There are four human coronaviruses (HCoVs) that circulate endemically across the globe; they cause only mild symptoms and are not a significant public health burden.”

The study suggests SARS-CoV-2 might join that group, but that it will take years and in the interim, the virus will continue to prove deadly.

“In the absence of vaccination or treatment,” the study warns, “high transmission is predicted to lead to a high caseload and death rate…(and) the total number of deaths is largely independent of the transmission rate (R0).”

In other words, the oft-discussed effort to flatten the bell-shaped curve of deadly infections doesn’t really do much on its own to reduce the number of deaths; it just spreads them out and buys time to, hopefully, develop treatments or the much-hoped-for vaccine that might reduce deaths in the future.

As the study puts it, “slowing down the epidemic through social distancing measures…(helps in) delaying infections and preventing the majority of deaths from happening early on, affording critical time for the development of an effective vaccine or treatment.

“However, as the time scales of disease spread and waning of immunity meet, transmission from reinfected individuals (likely asymptomatic or mild) to the vulnerable is predicted to increasingly drive excess deaths.”

This will continue, the study added, until the young people exposed to SARS-CoV-2 today become the bulk of the population tomorrow.

Once that happens, the study forecasts, “primary cases (will) occur almost entirely in babies and young children, who in the case of COVID-19, experience a low case-fatality rate (CFR). Reinfections in older individuals are predicted to be common and contribute to transmission, but in this steady-state population, older individuals, who would be at risk for severe disease from a primary infection, have acquired disease-reducing immunity following infection during childhood.”

Facebook of science

MedRxiv being the Facebook of science, the study has not been peer-reviewed and can only be considered as reliable as its authors. The corresponding author, Jennie Lavine at Emory, is a scientific consultant and writer with a PhD in biology.

She was joined in the work by Ottar N Bjornstad, who occupies the J. Lloyd & Dorothy Foehr Huck Chair of Epidemiology at Penn State, and Rustom Antia, a biology professor at Emory in Atlanta whose research has focused on pathogens and immune responses.

A year ago, Antia was one of a trio of scientists who published a peer-reviewed study of T-cell responses to viruses that in some ways foreshadowed what was to come with SARS-CoV-2.

“Some viral infections culminate in very different outcomes in different individuals,” the paper published by the Proceedings of the National Academy of Sciences of the United States of America said. “They can be rapidly cleared in some, cause persistent infection in others, and cause mortality from immunopathology in yet others. The conventional view is that the different outcomes arise as a consequence of the complex interactions between a large number of different factors (virus, different
immune cells, and cytokines).

“Here, we identify a simple dynamical motif comprising the essential interactions between antigens and CD8 T cells and posit it as predominantly determining the outcomes.”

Since then, SARS-CoV-2 has emerged; older people have proven highly vulnerable; and the weaker T-cell responses in the elderly have been blamed for SARS-CoV-2 putting them at high risk to death from COVID-19.

Chinese scientists posting at MedRxiv today reported finding that asymptomatic COVID-19 carriers – the sick people who don’t show symptoms –  “mounted potent virus-specific TH1 and CD8+ T cell responses” while in cases of moderate and severe disease “TH1 and CD8+ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in asymptomatic patients and revealed the strikingly dichotomous and unbalanced humoral and cellular immune responses in COVID-19 patients with different disease severity.”

“For many infectious diseases young children are most at risk,” Our World in Data, a website run by the University of Oxford notes. “(But) for COVID-19 cases the opposite seems to be true. The elderly are at the greatest risk of dying if infected with this virus.”

In all the countries where age-related deaths have been cataloged, the scale downward from under 0.3 percent for those younger than 40 to almost zero below age nine. But the trend is the opposite for those older than 40.

Death rates rise to 0.5 to 1.3 percent, depending on country, for people over age 50 and then start to skyrocket. Italy reports more than 20 percent of Italians 80 or older die if they come down with the disease, and though that age class does better in South Korea, the death rate is still 13 percent. Other countries fall between these numbers.

Endemic

The latest study hypothesizes what happens in the future based in large part on the difference in the way SARS-CoV-2 attacks the young and the old.

“As prospects for eradicating CoV-2 dwindle, we are faced with the question of how the severity of CoV-2 disease may change in the years ahead,” the authors write.

“Will CoV-2 continue to be a pathogenic scourge that, like smallpox or measles, can be tamed only by ongoing vaccination, or will it join the ranks of mild endemic human coronaviruses (HCoVs)? Our analysis
of immunological and epidemiological data on HCoVs shows that infection-blocking immunity wanes rapidly, but disease-reducing immunity is long-lived.”

The data, they said, indicates “all four (presently) endemic HCoV strains happen early in life; and our analysis of the data gives us an estimate for the mean age of primary infection between 3.4 and 5.1 years, with almost everyone infected by age 15.”

Given the high rates of infections in youth followed by regular reinfections in adults, they argue that it is pretty clear that the antibodies that provide infection-blocking immunity against HCoVs fade fairly quickly, but learned T-cell responses remain.

Essentially the theory is that overall T-cell immunity continues to decrease as people age, but once young T cells have learned to stave off SARS-CoV-2, they will carry that knowledge forward to be better equipped to fight the disease in old people.

“Our model recapitulates both the current severity of CoV-2 and the relatively benign nature of HCoVs; suggesting that once the endemic phase is reached, CoV-2 may be no more virulent than the common cold,” they write.

The suggestion that SARS-CoV-2 might become “no more virulent than the common cold” at some future time is likely to be controversial given that some believe any suggestion that things could or are getting better might diminish efforts to flatten the curve today.

Possibly even more controversial could be the study’s conclusion that its “results force us to re-evaluate control measures that rely on identifying and isolating symptomatic infections, and reconsider ideas regarding herd immunity and the use of immune individuals as shields to protect vulnerable groups.”

Herd immunity centers on the idea that once large numbers of people have been infected and survived, they essentially become invulnerable to the disease, and once a large number of people become invulnerable to the virus, it has a difficult time spreading because of the lack of cooperative, human hosts to carry it around.

Sweden – which pursued a more relaxed response to SARS-CoV-2 than the rest of the world because it may or may not have been trying to achieve herd immunity – has taken a beating in the media for even appearing to be pursuing the idea.

A few pundits have of late admitted to rethinking that view, but it is in general still portrayed as highly dangerous. CNN medical analyst Dr. Leana Wen, an emergency physician, said an attempt to reach herd immunity in the U.S. could kill 2 million people, although CNN International correspondent Max Foster in London was reporting “Sweden now has one of Europe’s lowest COVID-19 death rates.”

In the U.S., CNN has warned against a White House plot to pursue a goal of herd immunity with the claim that Dr. Scott Atlas, a member of the White House Coronavirus Task Force, has been “arguing that the administration should focus almost exclusively on protecting and testing elderly populations while pushing for the rest of the economy to return to normal, (an unnamed) official said.

“‘Everything he says and does points toward herd immunity,’ the senior administration official said.”

Dr. David L. Katz, the founding director of the Yale-Griffin Prevention Research Center at Yale University, suggested protecting the elderly and returning the rest of the country to as close to normal as a sensible idea in an op-ed in the New York Times back in March.

A short time later, a New York Times reporter appearing on CNN called the idea dangerous and demanded Katz apologize to the nation for writing the commentary.

Swedish national epidemiologist Anders Tegnell has admitted his country failed badly in protecting its elderly and thus drove up the COVID-19 death rate there.

But he told CNBC in May that Sweden has shown that “we can keep our schools open. That has not caused any major problems at all – it has not caused any problems that we can see. We can keep our society reasonably open, without huge effects.”

Sweden’s death rate from COVID-19 was at that time falling steadily, and it is now at low levels. Overall, Sweden at this time reports a death rate of 57.8 per 100,000 residents, according to Oxford’s Our World in Data; the U.S. rate is closed behind at 57 per 100,000. 

The U.S. number has been inflated by four states – New York, New Jersey, Massachusetts and Connecticut – with death rates two to more than three times greater than those of Sweden or the U.S. as a whole, according to the COVID-19 tracker at Statista. 

Thirty-eight states, as of this writing, are posting death rates below the national average for accidental deaths per 100,000, according to Statista. Wasington state, one of the first places to face the disease in the U.S., is among them with a death rate of 26 per 100,000.

Although the number of COVID-19 cases in Alaska has risen dramatically over the course of summer, according to State Department of Health and Social Services (DHSS) data, the Alaska COVID-19 death rate of 5 per 100,000 is now the lowest in the nation. It is about a fifth of the state’s suicide rate as reported by DHSS.

Whether the state organized the nation’s best response to COVID-19, was blessed with a low population that made social distancing relatively easy, or just got lucky is impossible to say, and whatever the case, the latest study indicates Alaska – and the rest of the world – is far from out of the woods yet.

“The findings presented here suggest that using symptoms as a surveillance tool to curb the virus’s spread will become more difficult as milder reinfections increasingly contribute to chains of transmission and population-level attack rates,” the authors write. “In addition, infection or vaccination may protect against disease but not provide the type of transmission-blocking immunity that allows for shielding or the generation of long-term herd immunity.”

The thought that a successful vaccine, if there is a successful vaccine, might protect those vaccinated but in the process lead to even more unidentifiable, asymptomatic carriers is not a pretty picture unless maybe you’ve invested heavily in companies producing face coverings.