The Next Wave of Severe COVID: A Prediction

A recent meeting of experts at the White House raised an ominous possibility.

On May 5, 2023, Dan Diamond of the Washington Post, wrote, “The White House recently received a sobering warning about the potential for the coronavirus to come roaring back…White House officials spoke with about a dozen leading experts in virology, immunobiology and other fields about the prospect that the virus would again develop mutations that allow it to evade protections from vaccines and treatments.”

Should we be worried?

I think the short answer to this question is “No.” To understand why, we need to go back to the beginning.

In December 2019, in Wuhan, China, a bat coronavirus entered the human population. By January 2020, the strain had been isolated, and its genome sequenced. It was called the Wuhan-1 or ancestral strain. All vaccines, including those made by Pfizer, Moderna, Johnson & Johnson, and Novavax, were designed to protect against this strain of virus. The Wuhan-1 strain, however, wasn’t the virus that left China. The strain that would soon travel the world—the very first variant—had one critical mutation that stabilized SARS-CoV-2 virus and made it ten times more contagious. This new variant didn’t have a Greek letter designation. It was called D614G.

In the United States, the D614G variant was soon replaced by the alpha variant, then the delta variant because each was more contagious. Then, at the end of 2021, a new variant called omicron reared its head. Omicron didn’t have only a handful of changes; it had 37 critical changes in the spike protein alone, far more than any previous variant. And omicron wasn’t just more contagious; it was more immune evasive. This meant that even if you had recently been vaccinated or naturally infected and had a high level of antibodies in your bloodstream, you still might get a mild COVID illness because those antibodies didn’t recognize the omicron variant particularly well.

But antibodies aren’t the whole story. There’s another part of the immune system that is critically important that most people don’t know about: T cells. T cells are divided into two groups: helper T cells, which help B cells make antibodies, and cytotoxic T cells, which kill virus-infected cells (“cytotoxic” means toxic to cells).

T cells are different than B cells. Unlike antibodies, T cells recognize parts of SARS-CoV-2 virus that are similar among all the different variants. Whereas new viral variants (like omicron) escaped recognition by antibodies, they didn’t escape recognition by T cells. That’s because the immunologically distinct regions (epitopes) recognized by T cells remained relatively stable (conserved) across variants from alpha to delta to omicron and continued to protect against serious disease.

Although antibodies induced by the vaccines made in 2020 weren’t very good at recognizing the omicron variants, T cells continued to recognize the new variants. This explains why, when omicron first entered the United States in late 2021, the number of cases of mild illness in people who had been vaccinated or previously infected was proportionally far greater than the number of COVID hospitalizations and deaths. For otherwise healthy young people, T cells continued to protect against severe disease; these cells weren’t fooled by the omicron variants. Only the antibodies were fooled.

Dan Barouch, an immunologist and virologist at Harvard Medical School, who spoke at that meeting in the White House, called T cells “the unsung heroes of the pandemic.” He explained that while variants like omicron had escaped recognition by antibodies, they hadn’t escaped recognition by T cells.

We have now suffered SARS-CoV-2 virus for more than three years. Variants have ranged from D614G to alpha, delta, omicron, gamma, epsilon, zeta, eta, theta, iota, kappa, lambda, and mu. No variant to date, however, has escaped recognition by T cells. And it might never happen. If it does; if a variant emerges that is resistant to both antibody and T cell responses, the entire population will once again be wholly susceptible to this virus. No one will be protected against serious illness. “Then we will be back at square one,” said Barouch. Everyone will need to be revaccinated to protect against this new variant.