Don’t freak out about Covid-19 reinfection stories

By Faye Flam
The most attention-grabbing scare stories about the pandemic often revolve around individual cases — someone who got the disease twice; a young, fit person who died; an older person who was likely infectious for more than two months. The fear is that these phenomena could be widespread, but scientists who study infectious disease say it’s normal to see extreme variability in the human reaction to any virus.

Early in the pandemic, people often described the disease based on their experience or someone they knew. Some said it was just the sniffles because that’s what they experienced. Others said it was the worst thing that ever hit them. They’re both right. But the over-generalization of these experiences can feed into the political polarization of the disease. It shouldn’t. In the big picture, Covid-19 neither the Black Death or the sniffles.

“There’s a vast diversity of immune responses as well as responses to infection,” says Dan Barouch, a vaccine researcher at Harvard Medical School. That’s the case with other pathogens from influenza to tuberculosis to HIV. “Sometimes it’s because of different genetics, and sometimes it’s from a different strain of the virus,” he says. “In some cases, it might be due to different viral doses or other immune parameters, or demographic variables — sometimes it comes down to chance.”

He said he’s not alarmed that there are a few documented cases of reinfection. Even if there are vastly more than the dozen or so reported reinfections, this would still represent a tiny sliver of the tens of millions of cases that have occurred worldwide.

One of the most striking examples, described in a case study in The Lancet, was a 25-year-old man in Nevada who was infected once in late March and later in May. Genetic analysis of the virus showed it was not a lingering effect of the same infection. While other cases of reinfection were milder the second time, this one was more severe.

It’s not all that surprising, says immunologist Florian Krammer of the Icahn School of Medicine at Mt. Sinai. The concentration of antibodies in different people infected with the virus follows something close to a bell curve, he says. There’s a typical response, but plenty of variation out at the edges. Sometimes people with more severe infections make more antibodies, but sometimes they see sky-high antibody concentrations in people who never get symptoms.

As millions of people become infected, it’s not surprising that a few get a new infection only a short time later, he says. In the Nevada case, the patient produced antibodies the second time, but possibly not the first. In another case out of Hong Kong, doctors measured a low antibody concentration after the first infection, and the patient had only a mild case the second time.

Another recent alarming case study described a 71-year-old woman with leukemia who never developed symptoms and never produced measurable antibodies, but appeared to remain infected and possibly infectious for more than 70 days — much longer than the eight days most patients are thought to be contagious.

Despite these exceptions, the experts I consulted still think most people will be immune for at least a few months after getting infected. And they expect that vaccines will work.

The immune system is complex and offers more defenses than only antibodies. Antibodies are produced during initial infection, says Krammer, but another component called memory B cells circulate in the body for years, retaining the ability to recognize the same virus and trigger a new immune response if it comes back.

Genes also play an intriguing role. Rheumatologist Arthur Krieg, the founder of Checkmate Pharmaceuticals, says that people with a defect in a gene called TLR7 can develop particularly severe cases of Covid-19. That gene regulates an all-purpose virus fighter called interferon, which is released quickly after exposure to pathogens.

According to an article in the Journal of the American Medical Association, the TLR7 gene is on the X chromosome, and that makes the problem much more common in males. (Females have two copies of the X chromosome, so are more likely to end up with at least one normal version of the gene.) In one case described in the article, two brothers in their early 20s were sick enough to need mechanical ventilation to survive. In another, a 32-year-old man and his 29-year-old brother were hospitalized, and the younger brother eventually died.

Another factor is experience with prior infections, says Krieg. There are four coronaviruses circulating in the population and causing common colds. He says exposure to these may influence the way people respond to Covid-19. Indeed, a new paper released Friday in Science shows that more than 5 percent of a sample of 302 people and more than 40 percent of a smaller group of children under 16 carried some immunity to the new coronavirus left over from these other infections.

In a study published in September in Science, a team led by Harvard geneticist Stephen Elledge showed people who got sick enough with Covid-19 to go to the hospital were much more likely to be infected with common herpes viruses CMV and HSV-1. These viruses are never completely cleared from the body. The researchers couldn’t tell whether these other viruses are making Covid-19 worse, or whether these people are more susceptible to viruses.

While there was some early thought that severity depended on how much virus you were exposed to — the so-called viral load — the experts said that was just a hypothesis. Disease severity may be more strongly influenced by factors that determine how easily the virus grows in your body once you’re infected — being exhausted or run down, for example. Environmental factors could also come into play; Krieg pointed to research led by Yale Immunologist Akiko Iwasaki showing that dry air might make the virus grow more readily in the nasal passages.

The variability in human response to the virus means there will likely be variability in the effectiveness of vaccines, he says, and that’s a good reason to try to gain public trust and get everyone on board. If enough people take a vaccine, the world could achieve herd immunity, even if the vaccine only worked in, say 70% of people. But if too few people get the vaccines, then even vaccinated people might not be safe, if they’re unlucky enough to be especially susceptible to the virus. And if that happens, we’ll all be living with Covid-19 for a long time to come.